ArticleLiterature Review

Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands—A review

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Abstract

Consuming the amino-acid tyrosine (TYR), the precursor of dopamine (DA) and norepinephrine (NE), may counteract decrements in neurotransmitter function and cognitive performance. However, reports on the effectiveness of TYR supplementation vary considerably, with some studies finding beneficial effects, whereas others do not. Here we review the available cognitive/behavioral studies on TYR, to elucidate whether and when TYR supplementation can be beneficial for performance. The potential of using TYR supplementation to treat clinical disorders seems limited and its benefits are likely determined by the presence and extent of impaired neurotransmitter function and synthesis. Likewise, the potential of TYR supplementation for enhancing physical exercise seems minimal as well, perhaps because the link between physical exercise and catecholamine function is mediated by many other factors. In contrast, TYR does seem to effectively enhance cognitive performance, particularly in short-term stressful and/or cognitively demanding situations. We conclude that TYR is an effective enhancer of cognition, but only when neurotransmitter function is intact and DA and/or NE is temporarily depleted.

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... Obviously, much work will be needed in order to determine the relative importance of altered brain tryptophan and other factors in controlling the mood and behavioral changes that occur after eating different foods.Tyrosine is a precursor to neurotransmitters, which include dopamine, norepinephrine, and epinephrine [Fernstrom, 2000]. Elevated levels of tyrosine increase the production of these neurotransmitters when our bodies need more of them [Jongkees et al., 2015). However, these situations have to be sufficiently challenging to require the extra release of neurotransmitters and subsequent depletion of these neurotransmitters. ...
... Tyrosine umol/dL Phenylanine umol/dL maintain optimal neural performance, tyrosine supplementations prevented the neurotransmitters from depleting (Jongkees et al., 2015).Data in table (1) and fig (1) agree with ( Cantoni et al., 1980& Cantoni et al., 1982Fernstrom, 2000;GU et al., 2012 andJongkees et al., 2015). Lower serum homocysteine concentrations were observed among those with higher Deficit Hyperactivity Disorder (DHA) in serum phospholipids in an apparently healthy Japanese population. ...
... Tyrosine umol/dL Phenylanine umol/dL maintain optimal neural performance, tyrosine supplementations prevented the neurotransmitters from depleting (Jongkees et al., 2015).Data in table (1) and fig (1) agree with ( Cantoni et al., 1980& Cantoni et al., 1982Fernstrom, 2000;GU et al., 2012 andJongkees et al., 2015). Lower serum homocysteine concentrations were observed among those with higher Deficit Hyperactivity Disorder (DHA) in serum phospholipids in an apparently healthy Japanese population. ...
... Given the strong dopaminergic involvement in WM, there has been great interest in enhancing WM function by manipulating the dopaminergic system. Studies have, for example, shown improved performance on WM-related tasks following administration of dopamine's precursors L-tyrosine (Jongkees, Hommel, Kühn, & Colzato, 2015;Jongkees et al., 2017) and L-dopa (Alavash et al., 2018;Eckart, Fuentemilla, Bauch, & Bunzeck, 2014), as well as the dopamine D2 receptor agonist bromocriptine (Gibbs & D'Esposito, 2005b;Wallace, Vytlacil, Nomura, Gibbs, & D'Esposito, 2011). However, there often is a lack of mechanistic insight into the neurocognitive basis of these effects; it frequently remains unclear which specific components of WM are affected by the dopaminergic manipulation. ...
... Extensive literature indicates that L-tyrosine is effective at inducing a modest increase in catecholaminergic activity (Jongkees et al., 2015). For example, administration of Ltyrosine previously increased plasma levels of dopamine's metabolite homovanillic acid in Parkinson's patients (Growdon, Melamed, Logue, Hefti, & Wurtman, 1982), as well as plasma levels of noradrenaline in healthy volunteers (Kishore et al., 2013). ...
... For example, administration of Ltyrosine previously increased plasma levels of dopamine's metabolite homovanillic acid in Parkinson's patients (Growdon, Melamed, Logue, Hefti, & Wurtman, 1982), as well as plasma levels of noradrenaline in healthy volunteers (Kishore et al., 2013). A broad literature has shown that Ltyrosine can reverse stress-induced impairment in WM performance (Jongkees et al., 2015), as well as enhancing performance without an external stressor when WM load is sufficiently high (Colzato et al., 2013;Jongkees et al., 2017;Thomas, Lockwood, Singh, & Deuster, 1999). L-tyrosine also has been shown to modulate the effect of noninvasive brain stimulation (Jongkees et al., 2017) in a manner that conceptually mirrored the effects of L-dopa (Kuo, Paulus, & Nitsche, 2008), as well as preexisting baseline differences in dopamine activity as predicted by the COMT Val158Met polymorphism (Plewnia et al., 2013). ...
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Article
Adaptive goal-directed behavior requires a dynamic balance between maintenance and updating within working memory (WM). This balance is controlled by an input-gating mechanism implemented by dopamine in the basal ganglia. Given that dopaminergic manipulations can modulate performance on WM-related tasks, it is important to gain mechanistic insight into whether such manipulations differentially affect updating (i.e., encoding and removal) and the closely-related gate opening/closing processes that respectively enable/prevent updating. To clarify this issue, 2.0 g of dopamine’s precursor L-tyrosine was administered to healthy young adults (N = 45) in a double-blind, placebo-controlled, within-subjects study. WM processes were empirically distinguished using the reference-back paradigm, which isolates performance related to updating, gate opening, and gate closing. L-tyrosine had a selective, baseline-dependent effect only on gate opening, which was evidenced by markedly reduced variance across subjects in gate opening performance in the L-tyrosine compared with the placebo condition, whereas the whole-sample average performance did not differ between conditions. This indicates a pattern of results whereby low-performing subjects improved, whereas high-performing subjects were impaired on L-tyrosine. Importantly, this inverted U-shaped pattern was not explained by regression to the mean. These results are consistent with an inverted-U relationship between dopamine and WM, and they indicate that updating and gating are differentially affected by a dopaminergic manipulation. This highlights the importance of distinguishing these processes when studying WM, for example, in the context of WM deficits in disorders with a dopaminergic pathophysiology.
... Tyrosine is a precursor of dopamine and noradrenaline and the administration of tyrosine stimulates synthesis and release of catecholamines [26][27][28][29][30]. The main source of tyrosine is protein-rich food, but tyrosine has also been administered selectively as an over-the-counter food supplement for study purposes and has been shown to alter cognition [31]. In young adults, tyrosine administration has been shown to improve cognitive control functions that are commonly associated with catecholamine transmission, such as working memory, response inhibition, and task switching [31,32]. ...
... The main source of tyrosine is protein-rich food, but tyrosine has also been administered selectively as an over-the-counter food supplement for study purposes and has been shown to alter cognition [31]. In young adults, tyrosine administration has been shown to improve cognitive control functions that are commonly associated with catecholamine transmission, such as working memory, response inhibition, and task switching [31,32]. ...
... The effects of tyrosine administration have been shown to depend on the baseline state of the system. For example, tyrosine was shown to be particularly effective in enhancing cognitive control when the catecholamine metabolism was enhanced by acute stress or high cognitive demand, while having no or disruptive effects in other conditions where the need for catecholamine transmission is lower [31,39]. Higher doses of tyrosine have been shown to increase plasma tyrosine concentrations to a greater degree in older than younger adults [40], and have been associated with poorer N-back performance than lower tyrosine doses [40]. ...
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Article
Catecholamines have long been associated with cognitive control and value-based decision-making. More recently, we have shown that catecholamines also modulate value-based decision-making about whether or not to engage in cognitive control. Yet it is unclear whether catecholamines influence these decisions by altering the subjective value of control. Thus, we tested whether tyrosine, a catecholamine precursor altered the subjective value of performing a demanding working memory task among healthy older adults (60–75 years). Contrary to our prediction, tyrosine administration did not significantly increase the subjective value of conducting an N-back task for reward, as a main effect. Instead, in line with our previous study, exploratory analyses indicated that drug effects varied as a function of participants’ trait impulsivity scores. Specifically, tyrosine increased the subjective value of conducting an N-back task in low impulsive participants, while reducing its value in more impulsive participants. One implication of these findings is that the over-the-counter tyrosine supplements may be accompanied by an undermining effect on the motivation to perform demanding cognitive tasks, at least in certain older adults. Taken together, these findings indicate that catecholamines can alter cognitive control by modulating motivation (rather than just the ability) to exert cognitive control.
... More recently, a number of studies have investigated the potential effect of the dopaminergic precursor tyrosine on cognitive flexibility, which theoretically might offer a number of advantages over L-Dopa. Unlike L-Dopa, the conversion of tyrosine to dopamine is restricted by competition from other endogenous amino acids and by the rate-limiting tyrosine-hydroxylase enzyme (Jongkees et al., 2015). These restrictions comparatively limit the overall enhancement of dopamine levels by tyrosine, and reduce the likelihood of shifting participants to the far end of the inverted U-shaped curve. ...
... Our group found that tyrosine had beneficial effects on set shifting, which was dependent on dorsolateral prefrontal cortex activity (Dennison et al., 2019). However, reports on the effectiveness of tyrosine on cognition are rather more inconsistent (Jongkees et al., 2015). Some of this heterogeneity is related to the clinical population tested (e.g. ...
... depression vs ADHD) (Gelenberg et al., 1990;Posner et al., 2009), and due to inter-individual differences of dopaminergic gene expression in the striatum (Colzato et al., 2016). Moreover, it has been suggested that the positive cognitive effects of tyrosine may be most prominent when individuals are exposed to stressful situations (Jongkees et al., 2015). ...
Article
Background: The catecholaminergic precursor to dopamine, tyrosine, is an important modulator of cognitive performance. A number of studies have demonstrated that the beneficial effects of tyrosine on cognitive performance are most pronounced when individuals are exposed to stressful situations, such as hypothermia. However, little is known about whether manipulation of stress using non-aversive stimuli, such as cognitive demand, can also bring about similar improvements. Methods: We conducted a randomized, double-blind, placebo-controlled experiment to test the effects of tyrosine administration and cognitive load (low or high) on cognitive flexibility, a measure known to be influenced by catecholaminergic function. A total of 70 healthy volunteers completed a baseline cognitive flexibility test (Wisconsin Card Sorting Test: WCST). Participants were given a dose of either tyrosine (2.0 g) or placebo (cellulose) and subject to either low cognitive load (simple reaction time task) or high cognitive load (digit memory span task), immediately followed by a WCST for a second time. Results: Contrary to expectations, we found that instead of ameliorating performance under the high cognitive load condition, tyrosine worsened cognitive flexibility. Limitations: Physiological marker of stress was not measured. Conclusions: Our results suggest that aversive stressors and cognitive demand modulate the effects of tyrosine on cognitive performance in a differential manner.
... Following testing, data from 4/48 participants were discarded due to extreme values (Z-scores = ±4) in the pre-drug and/or post-drug cognitive flexibility measurements, resulting in 11 participants in the tyrosine group, 12 in the GABA group, 10 in the tyrosine + GABA group, and 11 in the placebo group. The drugs were administered as a single dose in one session, in line with the vast majority of studies looking at the effects of short-term tyrosine on healthy populations reviewed elsewhere [39]. ...
... Tyrosine and GABA administration produce peak plasma concentrations at two different times. For tyrosine, the peak plasma concentration occurs at 60 min [39], whereas for GABA this happens at 30 min [32]. Thus, the tyrosine group first completed the cognitive flexibility tasks (T1, Figure 1C), then immediately received tyrosine, and were retested at 60 min post-drug administration (T2). ...
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Article
Increasing evidence, particularly from animal studies, suggests that dopamine and GABA are important modulators of cognitive flexibility. In humans, increasing dopamine synthesis through its precursor tyrosine has been shown to result in performance improvements, but few studies have reported the effects of GABA supplementation in healthy participants. We conducted a double-blind, placebo-controlled, randomized experiment to test the interactive effects of tyrosine and GABA administration on two measures of cognitive flexibility, response inhibition and task switching. A total of 48 healthy volunteers were split into four groups (placebo, tyrosine alone, GABA alone, and tyrosine and GABA combined). They completed cognitive flexibility tasks at baseline and after drug administration. We found that tyrosine alone had no impact on the measures of cognitive flexibility, whereas GABA alone and in combination with tyrosine worsened task switching. Our results provide preliminary evidence that putative increases in GABA and dopamine synthesis do not interact to affect cognitive flexibility performance.
... 127 Whilst APTD studies have used largely similar amino acids concentrations, the same cannot be said for tyrosine loading studies where dosages have varied from as little as 500 mg to 12 g. 128 Therefore, it is possible that the 50% reductions in plasma tyrosine levels by the APTD as reported by Sheehan and colleagues, 77 may not always be sufficient to create a dip in DA availability that is on the leftbottom side of the inverted-U curve. On the contrary, the combination of more varied dosages in tyrosine loading studies and the fact that tyrosine conversion to dopamine is limited by the competition from other endogenous amino acids and by the TH enzyme, means that even when higher dosages of tyrosine have been administered, these are unlikely to result in DA availability that is on the right-bottom side of the inverted-U curve. ...
... On the contrary, the combination of more varied dosages in tyrosine loading studies and the fact that tyrosine conversion to dopamine is limited by the competition from other endogenous amino acids and by the TH enzyme, means that even when higher dosages of tyrosine have been administered, these are unlikely to result in DA availability that is on the right-bottom side of the inverted-U curve. 128 Two studies by the Colzato group demonstrated an improvement in two separate measures of response inhibition by tyrosine supplementation when compared to a placebo group. 129,130 Similar results were obtained when measuring task switching. ...
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Article
The serotonergic precursor tryptophan and the dopaminergic precursor tyrosine have been shown to be important modulators of mood, behaviour and cognition. Specifically, research on the function of tryptophan has characterised this molecule as particularly relevant in the context of pathological disorders such as depression. Moreover, a large body of evidence has now been accumulated to suggest that tryptophan may also be involved in executive function and reward processing. Despite some clear differentiation with tryptophan, the data reviewed in this paper illustrates that tyrosine shares similar functions with tryptophan in the regulation of executive function and reward, and that these processes in turn, rather than acting in isolation, causally influence each other.
... Catecholamines, including dopamine, are important for working memory [14,15]. Several studies in young adults have shown that tyrosine administration can reverse working memory impairments under stressful conditions (for reviews, see [16,17]), or increase cognition, including working memory, in regular environmental conditions [18][19][20]. ...
... Other studies using the same 150 mg/kg body weight tyrosine dose in young adults, which gave adverse effects versus the 100 mg/kg body weight dose in our older adults, have shown beneficial effects of tyrosine on working memory performance (e.g. [32,38]).The currently observed decrements in working memory performance with increasing tyrosine dose in older adults might be surprising in the light of previous theories suggesting against dose-dependent effects in young adults [17,39]. However, the older adults showed markedly increased plasma tyrosine levels compared with the same dose in young adults, and this increase was associated with apparently paradoxical cognitive effects. ...
Preprint
The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150 or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210 and 240 minutes after tyrosine intake. Working memory was assessed using the N-back task at 90 minutes after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p<.001), and the plasma response was higher than for young adults with the same dose (p<.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p=.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p=.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.
... Its supplementation increases the circulating concentrations of these hormones in both the periphery and central nervous system [54]. When hormonal function is maintained intact, but dopamine and/or norepinephrine are temporarily depleted, tyrosine supplementation may enhance cognition [55]. Given the role of these hormones in motivation and thermoregulation [56][57][58][59][60][61], some research focus on the possible ergogenic activity of tyrosine on central fatigue and heat has been provided [62][63][64][65][66][67][68]. ...
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Article
The main aim of this study was to compare the performance over different distances, the critical velocity (CV), and plasma acylcarnitines/amino acids of male and female adolescent swimmers. Moreover, we applied the complex network approach to identify which molecules are associated with athletes’ performances. On the first day under a controlled environment, blood samples were collected after 12 h of overnight fasting. Performance trials (100, 200, 400, and 800-m) were randomly performed in the subsequent four days in a swimming pool, and CV was determined by linear distance versus time mathematical function. Metabolomic analyses were carried out on a triple quadrupole mass spectrometer performing electrospray ionization in the positive ionization mode. No difference was observed between the performance of male and female swimmers. Except for 200-m distance (p = 0.08), plasma tyrosine was positively and significantly associated with the female times during the trials (100-m, p = 0.04; 400-m, p = 0.04; 800-m, p = 0.02), and inversely associated with the CV (p = 0.02). The complex network approach showed that glycine (0.406), glutamine (0.400), arginine (0.335), free carnitine (0.355), tryptophan (0.289), and histidine (0.271) were the most influential nodes to reach tyrosine. These results revealed a thread that must be explored in further randomized/controlled designs, improving the knowledge surrounding nutrition and the performance of adolescent swimmers.
... Tyrosine and phenylalanine are precursors of serotonin, dopamine, epinephrine, and norepinephrine (Lakhan and Vieira 2008). Tyrosine supplements increase cognitive performance (Jongkees et al. 2015). β-Alanine is a natural neuromodulator AA present in the CNS (Tiedje et al. 2010). ...
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Chapter
Adequate food consumption of dietary nutrients is vital for normal brain functions. There is considerable proof that dietary nutrition helps in the cure and prevention of many psychiatric and neurological disorders. This chapter aims to highlight the effects of macronutrients, including fatty acids and amino acids, and micronutrients, including vitamins and minerals, on different brain functions such as neuronal functions, synaptic plasticity, memory, neuroinflammation, and neuronal signaling network. Furthermore, this chapter discusses the underpinning neuroprotective mechanisms of dietary nutrients, including antioxidant and anti-inflammatory effects, modulation of hypothalamic-pituitary-adrenal (HPA) axis, regulation of neurotransmitter synthesis, and neurotrophic functions. The highlighted relationships of dietary nutrients on brain functions in health and psychiatric diseases have revealed some of the critical mechanisms underpinning diet’s effect on brain health and will aid to control how best to utilize dietary nutrients to boost neuronal resistance to injuries and promote mental health.KeywordsNutritionBrain functionsAmino acidsMineralsVitaminsFatty acidsPUFA
... Three-hydroxybutyrate is considered as a promising target for deceleration of the ageing process, as increased levels of 3-hydroxybutyrate by e.g., dietary modulation are linked to decreased cellular ageing, suppression of inflammation and senescence, and improvement in metabolic homeostasis and neural regeneration [62]. Tyrosine is a non-essential amino acid that can be either gluconeogenic or ketogenic and is used in the melatonin synthesis [63]. Tyrosine level associates with mortality in patients with coronary artery disease [64], and alcohol consumption [58]. ...
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Article
Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex. cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts. In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.
... Tyrosine and Phenylalanine are precursor to each other. Tyrosine is an aromatic amino acid may help in treat depression, anxiety, lower body fat and plays an important role in production of thyroxin [17]. Though Phenylalanine is not recommended for people with phenylketonuria due to neurological disorders, it can be productive as a pain reliever in many cases [18]. ...
Article
Focussing on the need of sustainable diet, this research aimed to understand the nutritional feature of a traditional fermented beverage named as ‘Pendam’. As it is widely consumed in study region, participant observation method applied to understand the complete preparation process. In order to understand the quality of Pendam, the nutritional compositions were analysed using standard methods. With pH value of 3.6, this beverage reflects a protein and carbohydrate content of 1.614 mg/ml and 3.01 mg/ml respectively. Fat and yeast are absent in the beverage. The energy value stands at 1.8496 Cal/100 ml. Having cultural importance within the community, Pendam is considered sacred and play strong role in rituals and festivals. The nutritional features ensure it as a sustainable beverage.
... These neurotransmitters have the potential to assist people who are depressed. According to a review of considerable research, tyrosine may be helpful in treating mild-to-moderate depression [28].Tyrosine is found in dairy products, casein, meats, fish, eggs, nuts, beans, oats and wheat. Lysine: Out of the ten pigmented landraces Lysine was present in all samples, indicating the richness of lysine in pigmented rice landraces. ...
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Seeds accumulate proteins in protein storage vacuoles (PSVs) and these seed proteins undergo enzymatic denaturation by lipoxygenase and non-enzymatically by the oxidation of polyunsaturated fatty acids. Long-term storage can cause denaturation of seed storage proteins. Amino acids of cereal grains control the metabolism, diseases and play a crucial role in seed germination. The present study highlights the amino acid composition and germination efficiency in the stored seeds of pigmented rice landraces from the Kumaun region of India. All seed samples yielded 1.64µg/µl to 2.19µg/µl of total buffer soluble protein. Amino acid analyses performed by Whatman chromatography paper and the maximum number of amino acids were present in the ASP and APP1, i.e., four amino acids in each. Germination efficiency of ten colored rice landraces was also studied. When stored at a low temperature, no significant effect was observed.
... 45 Recent research showed that tyrosine shares similar functions with tryptophan in the regulation of CNS activity. 45,46 In our study, CF significantly affected the metabolism of L-dopa, dopaquinone, 3-methoxytyramine, gentisate aldehyde, and gentisic acid. Besides, thiamine (vitamin B1) is an essential nutrient that serves as a cofactor for mitochondrial localization. ...
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Article
The gut microbiome is known to be involved in depression development. Thus, phytochemicals changing gut microbiota may alleviate depression-like behaviors. Coniferyl ferulate (CF) is a long studied natural product and known to alleviate psychiatric disorders. However, its mechanism of action remains unclear. In this experimental study, oral administration of 50 mg kg −1 CF once daily attenuated weight loss and depression-like and anxiety-like behaviors induced by chronic unpredicted mild stress (CUMS) in mice. Four weeks of CF administration significantly ameliorated colonic inflammation, lowered the levels of IL-6, IL-1β, and TNF-α, and restructured the gut microbiome, and microbial metabolism. Intestinal micro-biota can impact the development and function of the brain via the microbiota-gut-brain axis. Therefore, oral administration of CF is a promising nutritional strategy to treat CUMS-induced depression via the regulation of microbiota and microbial metabolism.
... Tyrosine is an amino acid that is 460 used to relieve depression in clinical setting [45] . Recent research showed that tyrosine 461 shares similar functions with tryptophan in the regulation of CNS activity [45,46] . In our 462 study, CF significantly affected the metabolism of L-dopa, dopaquinone, 3- is an essential nutrient that serves as a cofactor for mitochondrial localization [47] . ...
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Article
The gut microbiome is known to be involved in depression development. Thus, phytochemicals changing gut microbiota may alleviate depression-like behaviors. Coniferyl ferulate (CF) is a long studied natural product and known to alleviate psychiatric disorders. However, its mechanism of action remains unclear. In this experimental study, oral administration of 50 mg kg-1 CF once daily attenuated weight loss and depression-like and anxiety-like behaviors induced by chronic unpredicted mild stress (CUMS) in mice. Four weeks of CF administration significantly ameliorated colonic inflammation, lowered the levels of IL-6, IL-1β, and TNF-α, and restructured the gut microbiome, and microbial metabolism. Intestinal microbiota can impact the development and function of the brain via the microbiota-gut-brain axis. Therefore, oral administration of CF is a promising nutritional strategy to treat CUMS-induced depression via the regulation of microbiota and microbial metabolism.
... Two main pathways are potentially involved, namely the vagus nerve and neurotransmitter production 8,27 . The role of the vagus nerve as the main nervous pathway from the ENS to the CNS 11,14,20 and the effects of the gut microbiota on the production of neurotransmitters are now well-established 14,20,25,43,44 . Nevertheless, we can only speculate, at this point, that the changes in gut microbiota affect decision making through these pathways, and the relative importance of each pathway in this neuronal network is still unclear 22 . ...
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Recent research has shown that the gut microbiota can influence the interaction between the central and the enteric nervous systems via the gut-brain axis (GBA). Animal models and human neuroimaging studies have revealed that changes in the gut microbiota affect neural activity in brain regions linked to basic emotional and cognitive processes. Whether the gut microbiota also affect human decision-making and, more specifically, risk and time preferences, however, remains largely unknown. Here, we examine the role of the gut-brain axis in decision-making in the face of risk and intertemporal choices. In a placebo-controlled double-blinded design, with two sessions separated by 28 days, during which participants received daily doses of probiotics (or a placebo), we investigate whether the prolonged and controlled intake of probiotics affects risk-taking behavior and intertemporal choices using incentivised economic tasks. We found a significant decrease in risk-taking behavior and an increase in future-oriented choices in the probiotics group as compared to the placebo group. These findings provided the first direct experimental evidence suggesting a potential functional role on the part of the microbiota-gut-brain axis in decision-making, creating a path for potential clinical applications and allowing for a better understanding of the underlying neural mechanisms of risk-taking behavior and intertemporal choices.
... Deficiency in noradrenaline associated with decreased alertness, problems of inattention, concentration and cognitive abilities may also arise from tyrosine deficiency. Dietary intake of tyrosine improves cognitive behavior in acute and chronic stress models (Jongkees et al., 2015;Alabsi et al., 2016), and this reduced stress effects may be due to the enhanced production of noradrenaline (McLean et al., 2004). ...
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Article
Depression is a serious mental and mood disorder with global health and economic burden. This burden may be overwhelming in low income countries, although there are insufficient data. Most antidepressant formulations are predicated on the monoamine, neuroendocrine and neuro-inflammation hypotheses, with little or no cognizance to other neurochemicals altered in depression. A nutritional strategy with or without conventional antidepressants is recommended, as nutrition plays vital roles in the onset, severity and duration of depression, with poor nutrition contributing to its pathogenesis. This review discusses nutritional potentials of utilizing omega-3 fatty acids, proteins, vitamins, minerals and herbs or their phytochemicals in the management of depression with the aim of reducing depression burden. Literature search of empirical data in books and journals in data bases including but not limited to PubMed, Scopus, Science Direct, Web of Science and Google Scholar that might contain discussions of sampling were sought, their full text obtained, and searched for relevant content to determine eligibility. Omega-3 fatty and amino acids had significant positive anti-depression outcomes, while vitamins and minerals although essential, enhanced omega-3 fatty and amino acids activities. Some herbs either as whole extracts or their phytochemicals/metabolites had significant positive anti-depression efficacy. Nutrition through the application of necessary food classes or herbs as well as their phytochemicals, may go a long way to effectively manage depression. This therefore will provide inexpensive, natural, and non-invasive therapeutic means with reduced adverse effects that can also be applied alongside clinical management. This nutritional strategy should be given more attention in research, assessment and treatment for those with depression and other mental illness in low income countries, especially in Africa.
... N-acetyl-L-tyrosine found in EAE improves cognitive function, as it acts as a precursor for dopamine. Oral N-acetyl-L-tyrosine is also reported increasing L-tyrosine levels in the brain (Jongkees et al., 2015;Topall and Laborit, 1989). a-Curcumene identified in EAE is reported as antibacterial and antifungal against selected microorganisms (Silva et al., 2015). ...
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Santolina chamaecyparissus is an important medicinal plant growing in the Mediterranean region and has been reported as a potent anti-inflammatory, antibacterial, antioxidant, and antifungal agent. The purpose of the current research is to identify the chemical constituents in ethyl acetate extract (EAE) from the leaves of S. chamaecyparissus, and to evaluate antidiabetic, and anticancer activity. Chemical constituents of EAE were identified by GC-MS, and the antidiabetic activity was evaluated by α-glucosidase inhibition assay. The anticancer activity was assessed by Epidermal Growth Factor Receptor (EGFR) expression in human breast cancer cell line (MCF7) by using quantitative RT-PCR method. GC-MS analysis of EAE of S. chamaecyparissus yielded 44 compounds. Tetrapentacontane (27.15%), eicosyl acetate (8.40%), 2-methylhexacosane (6.87%), and n-pentadecanol (5.44%) were found as major chemical constituents. The EAE of S. chamaecyparissus showed concentration dependant inhibition of α-glucosidase enzyme and the IC50 value (IC50 110±4.25 µg/mL) was found comparable with standard acarbose (IC50 105±3.74 µg/mL). The real-time qRT-PCR results showed that the EGFR protein (bcl-2) in human breast cancer cell line (MCF7) was negatively expressed with a value of -0.69297105 after treatment with EAE (100 µg/mL). The study results are suggesting the possible use of S. chamaecyparissus in the management of diabetes, and human breast cancer.
... Products made from soybeans [Glycine max]; may improve cognitive function in adults [98] St. Johns Wort [Hypericum perforatum], used for mild to moderate major depression, with moderate quality evidence and comparative effectiveness towards standard antidepressants [99] Tumeric, Curcumin [Curcuma longa], spice frequently used in Asian countries with anti-inflammatory and anti-oxidant properties with effects on depressive and anxiety symptoms [100] Tyrosine Amino acid, precursor of dopamine and noradrenaline, thyroid hormones, and melanin; reverses cognitive decline under stress or cognitive demands [101] Valerian [Valeriana officinalis], GABA-modulating phytochemical used as an anxiolytic [102] Vitamin B1 Thiamine, used for prevention of Wernicke-Korsakoff-syndrome in alcohol dependency disorders [103] Vitamin B3 Vitamin family that includes three forms or vitamers: nicotinamide (niacinamide), niacin (nicotinic acid), and nicotinamide riboside; deficiencies cause pellagra (fatigue, loss of appetite, abdominal pain), co-factor in serotonin-synthesis [104] Vitamin B-Complex Complex of water-soluable B-vitamins in food supplements ...
... Furthermore, the longterm potentiation (LTP) and tyrosine metabolism pathways involved in brain functions and neurotransmitter metabolism were also differentially abundant in high-vs. low-fatigue groups [44]. Taken together, our functional pathway results suggested that the gut microbiota could be linked to cancer treatment-related fatigue through their effects on inflammation and neuro-functions. ...
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Purpose Recent evidence supports a key role of gut microbiome in brain health. We conducted a pilot study to assess associations of gut microbiome with cancer-related fatigue and explore the associations with DNA methylation changes. Methods Self-reported Multidimensional Fatigue Inventory and stool samples were collected at pre-radiotherapy and one-month post-radiotherapy in patients with head and neck cancer. Gut microbiome data were obtained by sequencing the 16S ribosomal ribonucleic acid gene. DNA methylation changes in the blood were assessed using Illumina Methylation EPIC BeadChip. Results We observed significantly different gut microbiota patterns among patients with high vs. low fatigue across time. This pattern was characterized by low relative abundance in short-chain fatty acid–producing taxa (family Ruminococcaceae, genera Subdoligranulum and Faecalibacterium; all p < 0.05), with high abundance in taxa associated with inflammation (genera Family XIII AD3011 and Erysipelatoclostridium; all p < 0.05) for high-fatigue group. We identified nine KEGG Orthology pathways significantly different between high- vs. low-fatigue groups over time (all p < 0.001), including pathways related to fatty acid synthesis and oxidation, inflammation, and brain function. Gene set enrichment analysis (GSEA) was performed on the top differentially methylated CpG sites that were associated with the taxa and fatigue. All biological processes from the GSEA were related to immune responses and inflammation (FDR < 0.05). Conclusions Our results suggest different patterns of the gut microbiota in cancer patients with high vs. low fatigue. Results from functional pathways and DNA methylation analyses indicate that inflammation is likely to be the major driver in the gut-brain axis for cancer-related fatigue.
... Tyrosine supplementation seems to enhance cognitive performance, particularly in stressful situations. 76 The biogenic amines histamine and tyramine, present in stored or fermented foods, are active NTs in the brain per se, 77 binding to specific receptors. 78 ...
Article
The performance of the human brain is based on an interplay between the inherited genotype and external environmental factors, including diet. Food and nutrition, essential in maintenance of brain performance, also aid in prevention and treatment of mental disorders. Both the overall composition of the human diet and specific dietary components have been shown to have an impact on brain function in various experimental models and epidemiological studies. This narrative review provides an overview of the role of diet in 5 key areas of brain function related to mental health and performance, including: (1) brain development, (2) signaling networks and neurotransmitters in the brain, (3) cognition and memory, (4) the balance between protein formation and degradation, and (5) deteriorative effects due to chronic inflammatory processes. Finally, the role of diet in epigenetic regulation of brain physiology is discussed.
... Bibliografía: [217][218][219][220][221][222][223][224][225][226] Tópicos en nutrición y suplementación deportiva -Dr. Heber E. Andrada pág. ...
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This book is intended for anyone passionate about nutrition and sports supplementation. It aims to introduce readers to what regards the subject, combining areas such as nutrition, biological chemistry, the physiology of the exercise, food science and pharmacology. It is by no means intended to replace a good book on each of these areas, just try to give a general snapshot of each of the substances that are currently being used in the world of supplementation sports, its functions, applications, benefits and doses that are usually used. Heber E. Andrada October 5, 2020
... [93][94][95] Tyrosine and phenylalanine are also involved in the synthesis of dopamine and catecholamines that influence behavioral performance, with limited and inconsistent evidence that their supplementation is beneficial in the treatment of PWUD. 15,95,96 When patients dependent on heroin or opiates are given a combination of amino acids (namely, phenylalanine, tryptophan, tyrosine, and glutamine) while undergoing detoxification, they show a significant reduction in the craving for opiates. 97 This might be an important tool in the treatment of drug use that warrants additional study. ...
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A comprehensive overview is presented of the nutritional issues faced by people who use drugs or are undergoing treatment for recovery. Chronic substance use affects a person's nutritional status and body composition through decreased intake, nutrient absorption, and dysregulation of hormones that alter the mechanisms of satiety and food intake. Anthropometrics alone is not the best indicator of nutritional status, because this population has hidden deficiencies and disturbed metabolic parameters. Socioeconomic factors (eg, higher education, higher income, presence of a partner, living at home) positively affect nutritional status. Scarce available data on users undergoing treatment indicate improvement in anthropometric and metabolic parameters but with micronutrient intake remaining suboptimal. Weight gain is noted especially among women who use drugs and potentially increases their risk of relapse. Finally, specific amino acids and omega-3 fatty acids are promising in decreasing relapse and improving mental health during treatment; however, additional high-quality studies are needed. Nutrition intervention for people who use drugs or are undergoing treatment for recovery is underused; comprehensive programs addressing this population's unique needs are necessary. Future research will identify which components are needed.
... Although LABs possess enzymes for amino acids metabolism (Muyanja et al., 2012), co-metabolism between these LAB strains whereby, one strain can contribute to the formation of another compound by supplying substrates or intermediates for these compounds has recently been reported (Liu et al., 2017). Though naturally secreted, this compound may be deficient with clinical implication for the declined response of cognitive performance or several organ diseases, thus dietary supplement with the observed sample could potentially increase the compound bioavailability for physiological functions (Jongkees et al., 2015). ...
Article
Ting is a traditional fermented sorghum product mostly eaten in Southern Africa, generally believed to be highly nutritious and rich in health beneficial properties. Although refined grains are mostly used for fermented foods, the use of whole grains (WGs) in fermented products is gradually gaining prominence due to their benefits. In this study, Lactobacillus fermentum strains were used singly and in combination for the fermentation of WG-ting from WG-sorghum and all possible metabolites profiled using gas chromatography-high resolution time of flight-mass spectrometry.198 compounds were observed in the experimented samples, classified into different metabolic groups, with varying proportions: esters (23%), ketones (10%), fatty acids methyl esters (7%) and hydrocarbons (6%). Other important metabolites include vitamins, terpenes and terpenoids, phytosterols, phenols and alcohols. Although similar lactic acid bacteria were used, differences were observed in levels of the metabolites and in some instances, the types of metabolites obtained differ. Much of the differences were attributed to varying fermentation behaviors of the strains, which could be related to their inherent genes. The correlation between metabolites from raw sorghum and the fermented product may assist in developing processing methods to retain desired metabolites and enhance their functional potentials toward product improvement and for health benefits.
... The precursor for NE dopamine (DA) also inhibits adrenergic receptor signaling and blocks the synthesis of melatonin through α1B-D4 and β1-D4 receptor heteromers [71]. The supplementation of tyrosine has been used in many cognitive/behavioral studies but yielding significantly varied results [72]. Magill et al. reported that supplementation of tyrosine 150 mg/kg following overnight sleep deprivation improved working memory, reasoning, and vigilance [73]. ...
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Article
Sleep disorder significantly affects the life quality of a large number of people but is still an underrecognized disease. Dietary nutrition is believed to play a significant impact on sleeping wellness. Many nutritional supplements have been used trying to benefit sleep wellness. However, the relationship between nutritional components and sleep is complicated. Nutritional factors vary dramatically with different diet patterns and depend significantly on the digestive and metabiotic functions of each individual. Moreover, nutrition can profoundly affect the hormones and inflammation status which directly or indirectly contribute to insomnia. In this review, we summarized the role of major nutritional factors, carbohydrates, lipids, amino acids, and vitamins on sleep and sleep disorders and discussed the potential mechanisms.
... From the group of aromatic amino acids of our study, Tyr has been identified as the most important feature elevated in males when comparing to females in various analyses. Tyr has been found to enhance neurotransmitter synthesis in active neurons and, thus, may reverse the neurotransmitter depletion and benefit brain function [24]. Significantly elevated levels of amino acids, such as Phe or Tyr, have been associated with the increased risk of hyperglycemia [25] or diabetes mellitus type 2 [25,26]. ...
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The prevalence of some chronic diseases, such as cancer or neurodegenerative disorders, differs between sexes. Animal models provide an important tool to adopt potential therapies from preclinical studies to humans. Laboratory rats are the most popular animals in toxicology, neurobehavioral, or cancer research. Our study aimed to reveal the basic differences in blood metabolome (amino acids, biogenic amines, and acylcarnitines) of the adult male (n = 10) and female (n = 10) Wistar rats. Partial least square-discrimination analysis (PLS-DA) and a variance im portance in projection (VIP) score was used to identify the key sex-specific metabolites. All groups of metabolites, as the main markers of energy metabolism, showed a significant sex-dependent pattern. The most important features calculated in PLS-DA according to VIP score were free carnitine (C0), tyrosine (Tyr), and acylcarnitine C5-OH. While aromatic amino acids, such as Tyr and phenylalanine (Phe), were significantly elevated in the blood plasma of males, tryptophan (Trp) was found in higher levels in the blood plasma of females. Besides, significant sex-related changes in urea cycle were found. Our study provides an important insight into sex-specific differences in energy metabolism in rats and indicates that further studies should consider sex as the main aspect in design and data interpretation.
... Plays a critical role in the maintenance of intestinal mucosal integrity and barrier function [52] Tyrosine Oncorhynchus mykiss, Tor putitora Precursor of dopamine and norepinephrine [53] Valine ...
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Recent developments in nutraceuticals and functional foods have confirmed that bioactive components present in our diet play a major therapeutic role against human diseases. Moreover, there is a huge emphasis on food scientists for identifying and producing foods with better bioactive activity, which can ultimately provide wellness and well-being to human health. Among the several well-known foods with bioactive constituents, fish has always been considered important, due to its rich nutritional values and by-product application in food industries. Nutritionists, food scientists, and other scientific communities have been working jointly to uncover new bioactive molecules that could increase the potential and therapeutic benefits of these bioactive components. Despite the innumerable benefits of fish and known fish bioactive molecules, its use by food or pharmaceutical industries is scarce, and even research on fish-based nutraceuticals is not promising. Therefore, this review focuses on the current information/data available regarding fish bioactive components, its application as nutraceuticals for therapeutic purposes in the treatment of chronic diseases, ethnic issues related to consumption of fish or its by-products. Especial emphasis is given on the utilization of fish wastes and its by-products to fulfill the world demand for cheap dietary supplements specifically for underdeveloped/least developed countries.
... Microdialysis measures of DOPA or dopamine concentration in the rat striatum and medial prefrontal cortex are increased after L-tyrosine application (Brodnik et al., 2012(Brodnik et al., , 2017During, et al., 1989), indicating that dopamine availability can be increased by additional L-tyrosine. Effective systemic doses of L-tyrosine supplementation in humans vary between 500 and 12 g per day (for a review, see Jongkees et al., 2015). Recently, several studies by Colzato et al. have repeatedly shown cognitive effects on working memory and other tasks of executive function with 2 g of L-tyrosine supplementation (Colzato et al., 2013(Colzato et al., , 2016Jongkees et al., 2017;Steenbergen et al., 2015). ...
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Introduction and objectives The ability to adapt to new task demands flexibly and to stabilise performance in the presence of distractors is termed cognitive control and is mediated by dopaminergic and cholinergic neurotransmission. We aimed to test the hypothesis that the effect of the cholinergic agonist nicotine on cognitive control depends on baseline dopamine levels. Methods Thirty-eight healthy non-smokers (16 males; M age =24.05 years) performed a cognitive control task including distractor and switch trials twice. Subjects were split into two parallel groups. One group received 2 g of L-tyrosine two hours prior to testing to manipulate dopamine availability experimentally, while the other group received placebo on both days. One hour later, both groups received in a within-subject design: on one day, a 7 mg nicotine patch; on the other day, a matched placebo. Response time costs for distractor and switch trials served as measures of cognitive stability and flexibility. Results Nicotinic modulation reduced response time costs in switch trials and increased costs in distractor trials (nicotine×condition, p=0.027) with a trend-wise interaction between nicotine, L-tyrosine and trial type (nicotine×L-tyrosine×condition, p=0.068), which was due to stronger nicotine effects under L-tyrosine. Conclusions Our data provide preliminary evidence that nicotine has opponent effects on cognitive stability and flexibility. Subjects who received the dopamine precursor L-tyrosine were more prone to nicotine effects on behaviours, which are improvements in cognitive flexibility at the cost of decreased cognitive stability.
... Tyrosine is a non-essential amino acid that is used by cells to synthesise proteins. Briefly, tyrosine is found in high-protein food sources and is synthesised from phenylalanine [80]. Most importantly, tyrosine is the precursor for catecholamine synthesis, which occurs mainly in the brain or adrenal medulla. ...
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Intake of dietary supplements has increased, despite evidence that some of these have adverse side effects and uncertainty about their effectiveness. This systematic review examined the evidence for the cognitive benefits of a wide range of dietary supplements in healthy young adult samples; the aim was to identify if any might be useful for optimising cognitive performance during deployment in military personnel. Searches were conducted in 9 databases and 13 grey literature repositories for relevant studies published between January 2000 and June 2017. Eligible studies recruited healthy young adults (18–35 years), administered a legal dietary supplement, included a comparison control group, and assessed cognitive outcome(s). Thirty-seven of 394 identified studies met inclusion criteria and were included for synthesis. Most research was deemed of low quality (72.97%; SIGN50 guidelines), highlighting the need for sound empirical research in this area. Nonetheless, we suggest that tyrosine or caffeine could be used in healthy young adults in a military context to enhance cognitive performance when personnel are sleep-deprived. Caffeine also has the potential benefit of improving vigilance and attention during sustained operations offering little opportunity for sleep. Inconsistent findings and methodological limitations preclude firm recommendations about the use of other specific dietary supplements.
... It helps to balance nutrition in human body, however due to lack of sufficient L-tyrosine in food materials, it is added to various dairy products as well as pharmaceutical formulations [16,17]. Imbalance of L-tyrosine in the body causes several inborn diseases like hyperthyroidism, hypochondria, dementia, atherosclerosis or Parkinson [18,19]. Therefore, development of method(s) for detection of L-tyrosine, particularly at low concentration in aqueous media, is highly desirable. ...
Article
A calix[4]arene based compound incorporating amide and morpholine moieties has been synthesized and its ion recognition property towards metal ions and application of its metal complex towards sensing of amino acids has been investigated. The synthesized compound interacts with Cu2+ with high selectivity and sensitivity (LOD, 0.1 ppb) in aqueous media with instant color change from colorless to yellow without interference from any other metal ions used in this study. The molecular structure of the calix compound (1) has been determined by single crystal X-ray study and the structure of its Cu2+ complex has been established by DFT calculation. The Cu2+ complex of 1 selectively detects tyrosine (LOD, 1.2 ppm) in water with distinct color change and without any interference from other 22 amino acids used in this study. The mechanism for detection of tyrosine with color change is also presented. For easy field application, paper based sensor strips have been prepared by coating compound 1 and its Cu2+ complex on filter paper, which have been used for semi-quantitative measurement of Cu2+ and tyrosine. Compound 1 and its Cu2+ complex have also been used for detection of Cu2+ and tyrosine, respectively in water and human saliva as real samples and satisfactory results are obtained.
... There are good theoretical reasons for the use of tyrosine rather than L-Dopa. The conversion mechanism of tyrosine to dopamine and norepinephrine is restricted to by competition from other endogenous amino acids and by the rate-limiting tyrosine-hydroxylase enzyme whilst L-Dopa is not 31 . As a result, these restrictions would limit the overall enhancement in dopamine and norepinephrine levels from tyrosine. ...
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Animal studies have demonstrated that catecholamines regulate several aspects of fear conditioning. In humans, however, pharmacological manipulations of the catecholaminergic system have been scarce, and their primary focus has been to interfering with catecholaminergic activity after fear acquisition or expression had taken place, using L-Dopa, primarily, as catecholaminergic precursor. Here, we sought to determine if putative increases in presynaptic dopamine and norepinephrine by tyrosine administered before conditioning could affect fear expression. Electrodermal activity (EDA) of 46 healthy participants (24 placebo, 22 tyrosine) was measured in an instructed fear task. Results showed that tyrosine abolished fear expression compared to placebo. Importantly, tyrosine did not affect EDA responses to the aversive stimulus (UCS) or alter participants’ mood. Therefore, the effect of tyrosine on fear expression cannot be attributed to these factors. Taken together, these findings provide evidence that the catecholaminergic system influences fear expression in humans.
... It also helps in the production of melanin and in the function of organs in the body responsible for making and regulating hormones, including the adrenal, thyroid, and pituitary glands 23 . All these hormones regulate mood, therefore L-tyrosine is claimed to act as an effective antidepressant 24 . Tyrosine kinase signaling pathways are integral parts of the mammalian ovulatory process but do not involve actions on the synthesis of steroids, plasminogen activator or prostaglandins 25 . ...
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Objective: The aim of the study is to investigate the efficacy of a treatment with myoinositol plus L-tyrosine, selenium, and chromium in women with polycystic ovarian syndrome (PCOS). Patients and methods: One hundred and eighty-six women, with diagnosis of PCOS, were divided in four groups according to their clinical features. Phenotype A: androgen excess + ovulatory dysfunction + polycystic ovarian morphology. Phenotype B: androgen excess + ovulatory dysfunction. Phenotype C: androgen excess + polycystic ovarian morphology. Phenotype D: ovulatory dysfunction + polycystic ovarian morphology. All patients were given daily for six months a compound with 2 g myo-inositol, 0.5 mg L-Tyrosine, 0.2 mg folic acid, 55 mcg selenium, 40 mcg chromium. Hormonal assessment, BMI, Ferriman-Gallway Gallway score, HOMA index, and follicular monitoring were reported before starting the therapy, three months and six months after. Results: Phenotype A showed an improvement, consistent with restored ovulation: more regular length of the menstrual cycle, detection of periovulatory follicle at ultrasound, and rising of progesterone in the luteal phase. A total of 45 patients (65.2%) ovulated after six months. In the same period glucose and HOMA index decreased. In the phenotype B, 80% of patients ovulated after six months. An improvement of the clinical and biochemical sign of hyperandrogenism was also reported. In the phenotype C, after BMI had followed the treatment for six months, it decreased in a statistically significant manner. In the phenotype D, 49 out of 82 women (59.7%) restored their regular menstrual period and ovulated. Conclusions: Our study reported how the synergistic action of myoinositol, L-tyrosine, selenium, and chromium could restore normal menstrual cycle, ovulation, and decrease weight in these patients.
... However, another study found that supplementation of moderate tyrosine levels had no effect, while high dietary tyrosine levels decreased cognitive performance in older adults [362]. Authors of a recent review suggest that tyrosine supplementation likely only increases cognition during times of stress when either dopamine or norepinephrine levels are depleted [363]. There is no consistent data that tyrosine supplementation can decrease the effects of stress on cognitive or physical performance [364]. ...
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Article
Amino acids are the building blocks of protein, but also play important cellular signaling roles. The mechanisms through which altered levels of many amino acids are sensed and the signals transmitted are still largely unknown. Increasing evidence is showing that these signals may influence the aging process. In this regard, methionine restriction appears to be an evolutionary conserved mechanism to delay aging and supplementation with glycine can mimic methionine restriction to extend lifespan in rodents. Tryptophan restriction may also activate specific anti-aging pathways, but it could interfere with cognitive function. With exercise the consumption of dietary branched chain amino acids (BCAAs) may be beneficial in building muscle mass, but high levels of BCAAs as well as tyrosine and phenylalanine in the bloodstream are associated with metabolic disease such as insulin resistance. Individual supplementation or restriction of several different amino acids has shown promise in the treatment of insulin resistance in rodents. Much progress regarding the effects of amino acids on longevity has been made using yeast, nematodes, and fruit flies. Clearly, much more research is needed to understand the signaling pathways activated by amino acid imbalance before efficacious and well-tolerated dietary interventions can be developed for human aging and aging-related disorders. In this review the mechanisms through which altered dietary and cellular levels of the twenty proteogenic amino acids affect aging or aging-related disorders are discussed. Keywords: Amino acids, Aging, Lifespan, Yeast, C. elegans
... Taken together, a fair evaluation might be to conclude that one can observe effects of tyrosine on attentional tasks, but that these effects are small to unreliable, and more research is required to understand the conditions under which tyrosine works. Since a dosage of 1 to 2 g of tyrosine is the maximum of what has been recommended and used in previous studies (for a review, Jongkees et al. 2015), we cannot claim that tyrosine has widespread effects at the advised dosage. In addition, since tyrosine hydroxylase is one of the main limiting factors for DA and NE synthesis, higher doses exceeding 2 g are unlikely to exert additional beneficial effects. ...
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Article
The amino acid tyrosine is the precursor of dopamine and norepinephrine and can be administered as a dietary supplement. Previous studies have demonstrated that the intake of tyrosine can enhance both working memory performance and response inhibition (e.g., Colzato et al., Frontiers in Behavioral Neuroscience, 72013; Colzato et al., Neuropsychologia, 62, 398–402, 2014). In this study, we tested whether the consumption of tyrosine improved the performance of female participants in the Attention Network Test (ANT; Fan et al., Journal of Cognitive Neuroscience, 14, 340–347 2002) and the Stroop task (Stroop, Journal of Experimental Psychology, 18, 643–662 1935). Tyrosine marginally improved the resolution of interference in the Stroop task and had some impact on average reaction times. We conclude that more research is required as to understand the mechanisms through which tyrosine influences cognitive functioning. At this point in time, it remains unclear at best whether the consumption of tyrosine can be advised as a dietary supplement to support cognition.
Article
In this study, the cobalt and copper complexes of tyrosine (Tyr) were encapsulated in β-cyclodextrin (βCD) to improve their water solubility. The resulting inclusion complexes (Co-Tyr/βCD and Cu-Tyr/βCD) were characterized by FT-IR, UV–vis, EDX, ICP-OES, TGA, Cyclic Voltammetry (CV), and Photoluminescence (PL). TGA results indicated that approximately 35 wt.% and 41 wt.% of (Co+Tyr) and (Cu+Tyr) were encapsulated within the βCD cavity. The antioxidant activity of the samples was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. Co-Tyr/βCD was found to have better antioxidant activity than Cu-Tyr/βCD. The non-cytotoxic nature of the prepared samples was confirmed by the MTT assay.
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The blood-brain barrier (BBB) is the primary barrier with a highly selective semipermeable border between blood vascular endothelial cells and the central nervous system. Since BBB can prevent drugs circulating in the blood from crossing into the interstitial fluid of the brain where neurons reside, many researchers are working hard on developing drug delivery systems to penetrate the BBB which currently poses a challenge. Thus, blood-brain barrier penetrating peptides (B3PPs) are an alternative neurotherapeutic for brain-related disorder since they can facilitate drug delivery into the brain. In the meanwhile, developing computational methods that are effective for both the identification and characterization of B3PPs in a cost-effective manner plays an important role for basic reach and in the pharmaceutical industry. Even though few computational methods for B3PP identification have been developed, their performance might fail in terms of generalization ability and interpretability. In this study, a novel and efficient scoring card method-based predictor (termed SCMB3PP) is presented for improving B3PP identification and characterization. To overcome the limitation of black-box computational approaches, the SCMB3PP predictor can automatically estimate amino acid and dipeptide propensities to be B3PPs. Both cross-validation and independent tests indicate that SCMB3PP can achieve impressive performance and outperform various popular machine learning-based methods and the existing methods on multiple independent test datasets. Furthermore, SCMB3PP-derived amino acid propensities were utilized to identify informative biophysical and biochemical properties for characterizing B3PPs. Finally, an online user-friendly web server (http://pmlabstack.pythonanywhere.com/SCMB3PP) is established to identify novel and potential B3PP cost-effectively. This novel computational approach is anticipated to facilitate the large-scale identification of high potential B3PP candidates for follow-up experimental validation.
Chapter
Substance-use disorder (SUD) has become a global cause of morbidity and mortality and has an impact on general mental health. Substance users are mostly considered at high risk of nutritional deficiency, but most of the treatment centers do not provide any nutritional guide. The nutritional status of individuals in SUD needs to be properly addressed as it is responsible to cause malnutrition and making recovery more difficult. Hormonal alteration in SUD is the cause of low appetite and change in eating patterns, which leads to malnutrition. Furthermore, alterations in the absorption, utilization, metabolism, storage, distribution, and excretion of nutrients are responsible for nutritional deficiency. Micronutrient deficiency is reported in many of SUDs. Amino acid deficiency compromises the synthesis of neurotransmitters, which further exacerbates drug-seeking behavior. Moreover, craving for substances is altered by nutritional requirements, and the deprivation of food has shown to reduce the threshold for activation of reward pathways, which impedes recovery from SUD. During recovery, addiction transfer is a challenge in which patients start to crave for sweet food, which is also a cause of undernutrition and obesity. Hence, biopsychology of appetite and SUD can help to understand the causes of malnutrition. Therefore, in the recovery programs, planned nutrition can aid faster recovery and reduce the chances of food addiction and SUD relapse. Furthermore, alteration in dopaminergic and other brain pathways can also be considered via dietary intervention. It will not only be helpful in controlling the SUD, but also be beneficial for patient’s health.KeywordsSubstance-use disorderNutritionMalnutritionReward pathwayHormonesDietary intervention
Article
Objective The purpose of this study was to describe the management of 2 long-term users of cannabis with nutrition and psychotherapy. Clinical Features A 28-year-old man presented with a medical history of asthma, depression, anxiety, and smoking, and was a long-term user of cannabis for 9 years (usually 3 times a week). A 39-year-old man presented with a medical history of anxiety and fatigue, and was a long-term user of cannabis for 14 years (usually twice a week). Laboratory tests showed altered blood levels of homocysteine, vitamins, and cortisol. Intervention and Outcome Both patients were given supplements of vitamins (folic acid, methylcobalamin, and pyridoxine), vitamin D, Rhodiola rosea, and L-tyrosine. Psychotherapy also was provided to both patients. After 2 months of treatment, both patients improved and reduced their cannabis consumption. Conclusion This study describes vitamin deficiencies, low cortisol levels, and hyperhomocysteinemia in 2 cannabis users who were managed with a combination of nutritional supplements and psychotherapy.
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In recent times, the seafood industry is found to produce large volumes of waste products comprising shrimp shells, fish bones, fins, skins, intestines, and carcasses, along with the voluminous quantity of wastewater effluents. These seafood industry effluents contain large quantities of lipids, amino acids, proteins, polyunsaturated fatty acids, minerals, and carotenoids mixed with the garbage. This debris not only causes a huge wastage of various nutrients but also roots in severe environmental contamination. Hence, the problem of such seafood industry runoffs needs to be immediately managed with a commercial outlook. Microbiological treatment may lead to the valorization of seafood wastes, the trove of several useful compounds into value-added materials like enzymes, such as lipase, protease, chitinase, hyaluronidase, phosphatase, etc., and organic compounds like bioactive peptides, collagen, gelatin, chitosan, and mineral-based nutraceuticals. Such bioconversion in combination with a bio-refinery strategy possesses the potential for environment-friendly and inexpensive management of discards generated from seafood, which can sustainably maintain the production of seafood. The compounds that are being produced may act as nutritional sources or as nutraceuticals, foods with medicinal value. Determining utilization of seafood discard not only reduces the obnoxious deposition of waste but adds economy in the production of food with nutritional and medicinal importance, and, thereby meets up the long-lasting global demand of making nutrients and nutraceuticals available at a nominal cost.
Chapter
Practicing healthy and balanced diet is essential to ensure the body development. To date in spite of calories, focusing on food quality is much important as it plays a vital role in regulating the weight gain and loss. Foods that we intake has a vital impact on regulation of the brain parts. These have a strong relationship in either boosting or reducing the activity of central nervous system and peripheral nervous system. Nervous systems function and coordinate the body’s function with the help of electrical signals generated by neurons. Major constituent (proteins, carbohydrates, and fats) and minor constituent (minerals and vitamins) serve either as an energy source or precursor for neuroactive substances. Chemical signals are known as “neurotransmitters” that control the brain for any kind of responses. Neurotransmitters such as GABA (Gamma-aminobutyric acid), dopamine, serotonin, norepinephrine, and acetylcholine have a crucial effect in the brain’s functional activity. Dietary substance and supplements regulate such kind of neurotransmitters. Too high consumption of processed, packed food and other artificial additions led to physical and mental illness. This chapter discusses precisely on how different nutrients and types of diet are crucial in activating and deactivating the neural chemical signal.KeywordsNeurotransmittersNeuromodulatorsChemical signalExcitatoryInhibitory
Article
Amino acid neurotransmitters, including glutamate, phenylalanine, tyrosine, alanine, and glycine, underlie the majority of the excitatory and inhibitory neurotransmission in the nervous system, and acute exercise has been shown to modulate their concentrations. We aimed to determine whether any correlation exists between the above-mentioned amino acid blood concentrations and the neuropsychological performance after an acute exercise intervention. Sixty basketball players were randomly assigned to one of two experimental conditions: exercise or inactive resting. All participants underwent a comprehensive neuropsychological assessment and blood samples were taken on a Guthrie card before and after the end of the experimental conditions. Amino acid blood concentrations were significantly elevated and cognitive performance significantly improved post-exercise on specific neuropsychological assessments. Significant intervention × group interaction effects were apparent for Trail Making Test part-B [F(1,58) = 20.46, p < .0001, η2 = .26] and Digit Span Backwards [F(1,58) = 15.47, p < .0001, η2 = .21] neuropsychological assessments. Additionally, regression analysis indicated that tyrosine accounted for 38.0% of the variance in the Trail Making Test part-A test. These results suggest that elevated blood concentrations of neurotransmission-related amino acids are associated with improved neuropsychological performance after a single bout of high-intensity exercise.
Article
Ritonavir is a BCS class II antiretroviral agent which shows poor aqueous solubility and low oral bioavailability. The cocrystallization approach was selected to overcome these problems and to improve the physicochemical and mechanical properties of Ritonavir. The novel pharmaceutical Ritonavir-L-tyrosine cocrystals (RTC at a molar ratio of 1:1) were synthesized using the liquid assisted grinding (LAG) method. The possibility of molecular interactions between drug and coformer were studied using Gold software version 5.2. The newly formed crystalline solid phase was characterized through Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform-infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), and Solid-State Nuclear magnetic resonance (SSNMR). The improved pharmaceutical properties were confirmed by solubility, dissolution, and powder compaction study. The prepared cocrystals exhibited an 11.24-fold increase in solubility and a 3.73-fold increase in % of drug release at 1 h compared to pure drug. Tabletability and compaction behaviour of the pure drug and cocrystal with added excipients assessed. The tabletability profile of cocrystals showed enhanced tabletting performance as compared to pure drug. The stability studies revealed that cocrystals were stable for at least one month when stored at 40 °C/75% RH and 25 °C/60% RH conditions. The cocrystallization approach was found to be very promising and showed an overall improved performance of Ritonavir.
Article
Background Schizophrenia (SCZ) is a heterogeneous neuropsychiatric disorder, for which current treatment has insufficient efficacy and severe adverse effects. The modifiable gut microbiome might be a potential target for intervention to improve neurobiological functions through the gut-microbiome-brain axis. Methods In this case-control study, gut microbiota of 132 patients with SCZ and increased waist circumference was compared to gut microbiota of two age- and sex-matched control groups, comprising 132 healthy individuals (HC) and 132 individuals with metabolic syndrome (MS). Shotgun sequencing was used to characterize fecal samples at taxonomic and functional level. Cognition of the SCZ patients was evaluated using the Brief Assessment of Cognition instrument. Results SCZ gut microbiota differed significantly from those of HC and MS in terms of richness and global composition. SCZ gut microbiota was notably enriched in Flavonifractor plautii, Collinsella aerofaciens, Bilophila wadsworthia and Sellimonas intestinalis, while depleted in Faecalibacterium prausnitzii, Ruminococcus lactaris, Ruminococcus bicirculans and Veillonella rogosae. Functional potential of the gut microbiota accounted for 11% of the cognition variability. In particular, the bacterial functional module for synthesizing tyrosine, a precursor for dopamine, was in SCZ cases positively associated to cognitive score (rho = 0.34, q ≤ 0.1). Conclusions Overall, this study shows that the gut microbiome of SCZ patients differs greatly from that of healthy or MS controls. Cognitive function of SCZ patients is associated with the potential for gut bacterial biosynthesis of tyrosine, a precursor for dopamine, suggesting gut microbiota might be an intervention target for alleviation of cognitive dysfunction in SCZ.
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Macromolecules damaged by covalent modifications produced by chemically reactive metabolites accumulate in the slowly renewable components of living bodies and compromise their functions. Among such metabolites, catecholamines (CA) are unique, compared with the ubiquitous oxygen, ROS, glucose and methylglyoxal, in that their high chemical reactivity is confined to a limited set of cell types, including the dopaminergic and noradrenergic neurons and their direct targets, which suffer from CA propensities for autoxidation yielding toxic quinones, and for Pictet-Spengler reactions with carbonyl-containing compounds, which yield mitochondrial toxins. The functions progressively compromised because of that include motor performance, cognition, reward-driven behaviors, emotional tuning, and the neuroendocrine control of reproduction. The phenotypic manifestations of the resulting disorders culminate in such conditions as Parkinson’s and Alzheimer’s diseases, hypertension, sarcopenia, and menopause. The reasons to suspect that CA play some special role in aging accumulated since early 1970-ies. Published reviews address the role of CA hazardousness in the development of specific aging-associated diseases. The present integrative review explores how the bizarre discrepancy between CA hazardousness and biological importance could have emerged in evolution, how much does the chemical reactivity of CA contribute to the senescent phenotype in mammals, and what can be done with it.
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Objectives: The aim of this article is to explain the nutrients that play an active role in the pathophysiology of schizophrenia. Methods: This paper is a narrative literature review of relevant articles and prior works that have been central to the topic including the active nutrients in the pathophysiology of schizophrenia. Results: The findings are compiled under six headings. The changes in the antioxidant defense system, dopamine pathway, serotonin pathway, gamma-aminobutyric acid (GABA) pathway, glutamate pathway, the endocannabinoid system, and metabolomic profile were investigated in relation to nutrients. Conclusions: This review provides an update of scientific knowledge on the growing role of nutrition in schizophrenia. Nutrient deficiencies that occur frequently in these patients should be followed and eliminated to ensure the correct functioning of the pathophysiological pathways of the disease.
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Objective: To evaluate the effect of feeding via percutaneous endoscopic gastrostomy tube (PEG) on serum amino acid levels and mortality. Study design: Descriptive study. Place and duration of study: University of Health Sciences, Umraniye Training and Research Hospital, Istanbul, Turkey, from January 2016 to February 2019. Methodology: Patients over 18 years of age, who were indicated for PEG due to loss of swallowing reflex, were included in the study. The follow-up period of the study was one year. The patients were reevaluated on the 3rd, 6th, and 12th months after inclusion. Anthropometric measurements, and nutritional status were evaluated at each visit, and quantitative amino acid levels were analysed. Statistical significance was accepted as p <0.05. Results: The study was carried out with a total of 53 cases (23 men and 30 women) ranging in the age from 18 to 91 years. While 13 patients were still alive, 40 patients died before completing one year. The levels of glutamine, leucine, taurine, and threonine were significantly different between surviving patients and dead. A statistically significant difference was found between the levels of citrulline (p <0.001), ornithine (p = 0.036) and tyrosine (p = 0.011) during the four different visits of patients who survived. In patients who died, a significant difference was found between the levels of threonine, ornithine, and aspartic acid (p <0.043 for all) between visits. Citrulline and tyrosine levels were found to be significantly increased in surviving patients. Conclusion: The amino acid profiles of malnourished patients vary considerably. Increase in citrulline, ornithine and tyrosine levels are noted in surviving patients. Key Words: Amino acid, Percutaneous endoscopic gastrostomy, Malnutrition, Mortality.
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Sources of nutrients, especially essential amino acids that can not be produced by the body are needed. Several types of termites have been consumed by the community, one of which is Macrotermes gilvus . The purpose of this study was to analyze amino acids in Macrotermes gilvus soil termite colonies. The instrument used for analysis was High Pressure Liquid Chromatography (HPLC). The results showed that most amino acids originated from the neotene Macrotermes gilvus compared to the queen and king. The termite queen has a higher amino acid content than the king. The dominant amino acid in queens, kings and neotenes is serine, while the very limited amino acid is methionine. Based on this, Macrotermes gilvus soil termite colonies can be used as an alternative source of protein that rice of essential amino acid.
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Purpose: Tyrosine administration may counter exercise fatigue in a warm environment, but the typical dose is inconclusive, with little known about higher doses. We explored how three tyrosine doses influenced the circulating ratio of tyrosine: amino acids competing for brain uptake, and hypothesised a medium and high dose would enhance exercise performance in a warm environment. Methods: Eight recreationally trained, non-heat acclimated males [mean (± SD) age, 23 ± 4 years; stature, 181 ± 7 cm; body mass, 76.1 ± 5.9 kg; peak oxygen uptake (V[Combining Dot Above]O2peak), 4.1 ± 0.5 L·min] performed a V[Combining Dot Above]O2peak test, two familiarisation trials, then four experimental trials in a randomised order separated by 7 d. Prior to exercise, subjects drank 2 x 300 mL sugar-free drinks delivering zero (PLA), 150 (LOW), 300 (MED) or 400 (HIGH) mg·kg body mass tyrosine in a double-blind fashion. Subjects performed 60 min constant intensity cycling then a simulated time trial in 30°C and 60% relative humidity. Results: Time trial performance (P = 0.579) was not influenced by tyrosine ingestion. The plasma ratio of tyrosine: ∑(free-tryptophan, leucine, isoleucine, valine, phenylalanine, methionine), a key determinant of brain tyrosine influx, increased relative to PLA (P < 0.001). The increase was similar (P > 0.05) in MED (7.7-fold) and HIGH (8.2-fold), and greater than LOW (5.3-fold; P < 0.05). No differences existed between trials in core and skin temperature, heart rate, RPE or thermal sensation (P > 0.05). Conclusion: Exercise performance in a warm environment was not influenced by tyrosine availability in recreationally trained males. The results provide novel data informing future studies, on the tyrosine dose maximising the circulating ratio of tyrosine: amino acids competing for brain uptake.
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The yolk-shell structured SnO2-C nanospheres have been prepared by a hydrothermal reaction of SnCl2•2H2O and glucose, followed by carbonization under 500 °C in air condition. Then an inorganic/organic hybrid film bearing SnO2-C and polytyrosine (pTyr) is fabricated by electro-polymerization of SnO2-C modified electrode in tyrosine solution. The modified electrode is utilized as a supporting platform for covalent immobilization of cauliflower mosaic virus 35s (CaMV35s) promoter gene fragments to construct an electrochemical DNA sensor. Chronocoulometric experiments show that the loading density of probe DNA (pDNA) and hybridization efficiency are determined to be as high as 4.54×1013 strands cm–2 and 83.2%, respectively. Upon hybridization with target DNA (tDNA), the probe DNA that lied flat on the electrode surface through hydrogen bonding with pTyr is erected, reducing the charge repulsion and steric hindrance for [Fe(CN)6]3−/4− diffusion. So a “signal-off” response strictly dependent on hybridization reaction is achieved in electrochemical impedance spectroscopy. The response mechanism is predicted by theoretical calculation. Owing to the high probe density and hybridization efficiency of the sensor, a wide kinetic linear ranging from 1.0 aM to 100 pM and an ultralow detection limit of 0.53 aM for target sequence are obtained. The biosensor also presents high recognition ability toward the DNA samples extracted from real transgenic and non-transgenic soybeans, showing great promising of the biosensor for facile monitoring of transgenic product.
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To test the efficacy of tyrosine supplementation, as an adjunct to dietary treatment, on neuropsychological test performance in individuals with phenylketonuria. A randomised controlled trial of tyrosine supplementation using a double blind crossover procedure with three four week phases. The Hospital for Sick Children, Toronto. 21 individuals with phenylketonuria (ages 6 to 28 years, mean 11.3). Participants were given 100 mg/kg body weight/d of L-tyrosine or L-alanine (placebo). At baseline, performance on several of the neuropsychological test measures was correlated with tyrosine levels. Dietary supplements of tyrosine increased plasma tyrosine concentrations; however, no change in test performance was found across the tyrosine and placebo phases of the study. Tyrosine supplementation of this type does not appear to alter neuropsychological performance in individuals with phenylketonuria.
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Multiple lines of evidence suggest a deficit in dopamine release in the prefrontal cortex (PFC) in schizophrenia. Despite the prevalence of the concept of prefrontal cortical hypodopaminergia in schizophrenia, in vivo imaging of dopamine release in the PFC has not been possible until now, when the validity of using the positron emission tomographic D2/3 radiotracer carbon 11-labeled FLB457 in combination with the amphetamine paradigm was clearly established. To (1) test amphetamine-induced dopamine release in the dorsolateral PFC (DLPFC) in drug-free or drug-naive patients with schizophrenia (SCZ) and healthy control (HC) individuals matched for age, sex, race/ethnicity, and familial socioeconomic status;(2) test blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging activation during a working memory task in the same participants; and (3) examine the relationship between positron emission tomographic and functional magnetic resonance imaging outcome measures. Positron emission tomographic imaging with carbon 11-labeled FLB457 before and following 0.5 mg/kg of amphetamine by mouth. Blood oxygenation level-dependent functional magnetic resonance imaging during the self-ordered working memory task. Twenty patients with schizophrenia recruited from the inpatient and outpatient research facilities at New York State Psychiatric Institute and 21 healthy control individuals participated, and data were acquired between June 16, 2011, and February 25, 2014. The percentage change in binding potential (∆BPND) in the DLPFC following amphetamine, BOLD activation during the self-ordered working memory task compared with the control task, and the correlation between these 2 outcome measures. We observed significant differences in the effect of amphetamine on DLPFC BPND (mean [SD], ∆BPND in HC: -7.5% [11%]; SCZ: +1.8% [11%]; P = .01); a generalized blunting in dopamine release in SCZ involving most extrastriatal regions and the midbrain; and a significant association between ∆BPND and BOLD activation in the DLPFC in the overall sample including patients with SCZ and HC individuals. To our knowledge, these results provide the first in vivo evidence for a deficit in the capacity for dopamine release in the DLPFC in SCZ and suggest a more widespread deficit extending to many cortical and extrastriatal regions including the midbrain. This contrasts with the well-replicated excess in dopamine release in the associative striatum in SCZ and suggests a differential regulation of striatal dopamine release in associative striatum vs extrastriatal regions. Furthermore, dopamine release in the DLPFC relates to working memory-related activation of this region, suggesting that blunted release may affect frontal cortical function.
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The glutamate and dopamine hypotheses are leading theories of the pathoaetiology of schizophrenia. Both were initially based on indirect evidence from pharmacological studies supported by post-mortem findings, but have since been substantially advanced by new lines of evidence from in vivo imaging studies. This review provides an update on the latest findings on dopamine and glutamate abnormalities in schizophrenia, focusing on in vivo neuroimaging studies in patients and clinical high-risk groups, and considers their implications for understanding the biology and treatment of schizophrenia. These findings have refined both the dopamine and glutamate hypotheses, enabling greater anatomical and functional specificity, and have been complemented by preclinical evidence showing how the risk factors for schizophrenia impact on the dopamine and glutamate systems. The implications of this new evidence for understanding the development and treatment of schizophrenia are considered, and the gaps in current knowledge highlighted. Finally, the evidence for an integrated model of the interactions between the glutamate and dopamine systems is reviewed, and future directions discussed. © The Author(s) 2015.
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Anecdotal evidence suggests that creative people sometimes use food to overcome mental blocks and lack of inspiration, but empirical support for this possibility is still lacking. In this study, we investigated whether creativity in convergent- and divergent-thinking tasks is promoted by the food supplement L-Tyrosine (TYR)-a biochemical precursor of dopamine, which is assumed to drive cognitive control and creativity. We found no evidence for an impact of TYR on divergent thinking ("brainstorming") but it did promote convergent ("deep") thinking. As convergent thinking arguably requires more cognitive top-down control, this finding suggests that TYR can facilitate control-hungry creative operations. Hence, the food we eat may affect the way we think.
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In this study we tested the idea that the food supplement l-Tyrosine (TYR) repletes resources required for cognitive-control operations. We investigated whether the "updating" (and monitoring) of working memory (WM) representations, a key cognitive-control function, can be promoted by administering TYR, the biochemical precursor of dopamine. Participants performed an N-back task where we compared the WM-demanding 2-back condition with the WM-undemanding 1-back condition. As expected, TYR promoted performance in the more demanding (2-back) but not in the easier (1-back) condition, suggesting that TYR selectively targets cognitive-control operations. This result suggests that TYR can replete cognitive resources when more control is needed and, more generally, that food can act as a cognitive enhancer.
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Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans.
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Attention-deficit/hyperactivity disorder (ADHD) is a commonly diagnosed childhood disorder characterized by impulsivity, inattention, and hyperactivity. ADHD affects up to 1 in 20 children in the United States. The underlying etiologies of ADHD may be heterogeneous and diverse, and many possible risk factors in the development of ADHD have been identified. Conventional treatment usually consists of behavioral accommodations and medication, with stimulant medication most commonly being prescribed. Parents concerned about the side effects and long-term use of conventional medications are increasingly seeking alternatives to pharmacologic treatment. Complementary and alternative medicine (CAM) offers parents various treatment options for this condition, including dietary modifications, nutritional supplementation, herbal medicine, and homeopathy. CAM appears to be most effective when prescribed holistically and according to each individual's characteristic symptoms. Possible etiologies and risk factors for the condition also need to be considered when developing a treatment plan. This article serves to highlight the latest research regarding the most commonly used CAM for children with ADHD.
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Increased brain dopamine availability improves prolonged exercise tolerance in the heat. It is unclear whether supplementing the amino-acid precursor of dopamine increases exercise capacity in the heat. Eight healthy male volunteers [mean age 32 ± 11 (SD) years; body mass 75.3 ± 8.1 kg; peak oxygen uptake ([Formula: see text]) 3.5 ± 0.3 L min(-1)] performed two exercise trials separated by at least 7 days in a randomised, crossover design. Subjects consumed 500 mL of a flavoured sugar-free drink (PLA), or the same drink with 150 mg kg body mass(-1) tyrosine (TYR) in a double-blind manner 1 h before cycling to exhaustion at a constant exercise intensity equivalent to 68 ± 5% [Formula: see text] in 30°C and 60% relative humidity. Pre-exercise plasma tyrosine:large neutral amino acids increased 2.9-fold in TYR (P < 0.01), while there was no change in PLA (P > 0.05). Subjects cycled longer in TYR compared to PLA (80.3 ± 19.7 min vs. 69.2 ± 14.0 min; P < 0.01). Core temperature, mean weighted skin temperature, heart rate, ratings of perceived exertion and thermal sensation were similar in TYR and PLA during exercise and at exhaustion (P > 0.05) despite longer exercise time in TYR. The results show that acute tyrosine supplementation is associated with increased endurance capacity in the heat in moderately trained subjects. The results also suggest for the first time that the availability of tyrosine, a nutritional dopamine precursor, can influence the ability to subjectively tolerate prolonged submaximal constant-load exercise in the heat.
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Tyrosine hydroxylase is the rate-limiting enzyme of catecholamine biosynthesis; it uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to DOPA. Its amino terminal 150 amino acids comprise a domain whose structure is involved in regulating the enzyme's activity. Modes of regulation include phosphorylation by multiple kinases at four different serine residues, and dephosphorylation by two phosphatases. The enzyme is inhibited in feedback fashion by the catecholamine neurotransmitters. Dopamine binds to TyrH competitively with tetrahydrobiopterin, and interacts with the R domain. TyrH activity is modulated by protein-protein interactions with enzymes in the same pathway or the tetrahydrobiopterin pathway, structural proteins considered to be chaperones that mediate the neuron's oxidative state, and the protein that transfers dopamine into secretory vesicles. TyrH is modified in the presence of NO, resulting in nitration of tyrosine residues and the glutathionylation of cysteine residues.
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Notwithstanding the success of the traditional dietary phenylalanine restriction treatment in phenylketonuria (PKU), the use of large neutral amino acid (LNAA) supplementation rather than phenylalanine restriction has been suggested. This treatment modality deserves attention as it might improve cognitive outcome and quality of life in patients with PKU. Following various theories about the pathogenesis of cognitive dysfunction in PKU, LNAA supplementation may have multiple treatment targets: a specific reduction in brain phenylalanine concentrations, a reduction in blood (and consequently brain) phenylalanine concentrations, an increase in brain neurotransmitter concentrations, and an increase in brain essential amino acid concentrations. These treatment targets imply different treatment regimes. This review summarizes the treatment targets and the treatment regimens of LNAA supplementation and discusses the differences in LNAA intake between the classical dietary phenylalanine-restricted diet and several LNAA treatment forms.
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Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct stressful stimuli.
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To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity.
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Background: Recent research on schizophrenia indicates that cognitive deficits in this illness are important predictors of functional outcome, highlighting the need for treatments that have a positive impact on cognitive function. Here we explore the hypothesis that acute administration of D-amphetamine can improve cognitive function in individuals with schizophrenia who are well-treated with typical antipsychotics, as well as in healthy controls performing under dual task conditions designed to elicit performance deficits analogous to those found in schizophrenia. Methods: Ten individuals with schizophrenia taking haldol or prolixin and 22 healthy controls performed spatial working memory, language production, and Stroop tasks under both placebo and 0.25 mg/kg of D-amphetamine. Results: D-Amphetamine improved reactions times on the spatial working memory and Stroop tasks for both individuals with schizophrenia and controls, and improved working memory accuracy in schizophrenia. In addition, D-amphetamine improved language production for both individuals with schizophrenia and controls. Conclusions: These results provide support for the hypothesis that the adjunctive administration of dopamine agonist can improve cognitive in individuals with schizophrenia taking typical antipsychotics. The results are discussed in terms of their implications for understanding the nature of working memory deficits in schizophrenia, and potential future avenues for cognitive enhancement in this illness. (c) 2005 Elsevier B.V. All rights reserved.
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Parkinson's disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Current PD medications treat symptoms; none halt or retard dopaminergic neuron degeneration. The main obstacle to developing neuroprotective therapies is a limited understanding of the key molecular events that provoke neurodegeneration. The discovery of PD genes has led to the hypothesis that misfolding of proteins and dysfunction of the ubiquitin-proteasome pathway are pivotal to PD pathogenesis. Previously implicated culprits in PD neurodegeneration, mitochondrial dysfunction and oxidative stress, may also act in part by causing the accumulation of misfolded proteins, in addition to producing other deleterious events in dopaminergic neurons. Neurotoxin-based models (particularly MPTP) have been important in elucidating the molecular cascade of cell death in dopaminergic neurons. PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.
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Tyrosine (TYR), an amino acid found in various foods, has been shown to increase dopamine (DA) levels in the brain. Recent studies have provided evidence that TYR supplementation can improve facets of cognitive control in situations with high cognitive demands. Here we investigated whether TYR promotes cognitive flexibility, a cognitive-control function that is assumed to be modulated by DA. We tested the effect of TYR on proactive vs. reactive control during task switching performance, which provides a relatively well-established diagnostic of cognitive flexibility. In a double-blind, randomized, placebo-controlled design, 22 healthy adults performed in a task-switching paradigm. Compared to a neutral placebo, TYR promoted cognitive flexibility (i.e. reduced switching costs). This finding supports the idea that TYR can facilitate cognitive flexibility by repleting cognitive resources.
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Animal studies and research in humans have shown that the supplementation of tyrosine, or tyrosine-containing diets, increase the plasma tyrosine and enhance brain dopamine (DA). However, the strategy of administering tyrosine (and the role of DA therein) to enhance cognition is unclear and heavily debated. We studied, in a healthy population, whether tyrosine supplementation improves stopping overt responses, a core cognitive-control function. In a double-blind, placebo-controlled, within-subject design, one hour following the administration of tyrosine (corresponding to the beginning of the 1h-peak of the plasma concentration) or placebo, participants performed a stop-signal task-which taps into response inhibition and response execution speed. Participants in the tyrosine condition were more efficient in inhibiting unwanted action tendencies but not in reacting to go signals. This is the first demonstration that the supplementation of tyrosine selectively targets, and reliably improves the ability to stop overt responses.
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Acute oral tyrosine administration has been associated with increased constant-load, submaximal exercise capacity in the heat. This study sought to determine whether self-paced exercise performance in the heat is enhanced with the same tyrosine dosage. Following familiarisation, seven male endurance-trained volunteers, unacclimated to exercise in the heat, performed two experimental trials in 30°C (60% relative humidity) in a crossover fashion separated by at least 7 days. Subjects ingested 150 mg·kg body mass tyrosine (TYR) or an isocaloric quantity of whey powder (PLA) in 500 mL of sugar-free flavoured water in a randomised, double-blind fashion. Sixty minutes following drink ingestion subjects cycled for 60 min at 57 ± 4% peak oxygen uptake (O2peak), then performed a simulated cycling time-trial requiring completion of an individualised target work quantity (393.1 ± 39.8 kJ). The ratio of plasma tyrosine plus phenylalanine (tyrosine precursor): amino acids competing for brain uptake (free-tryptophan, leucine, isoleucine, valine, methionine, threonine, lysine) increased 2.5-fold from rest in TYR, and remained elevated throughout exercise (P < 0.001), whereas it declined in PLA from rest to pre-exercise (P = 0.004). Time-trial power output (P = 0.869) and performance (34.8 ± 6.5 min and 35.2 ± 8.3 min in TYR and PLA, respectively; P = 0.4167) were similar between trials. Thermal sensation (P > 0.05), RPE (P > 0.05), core temperature (P = 0.860), skin temperature (P = 0.822) and heart rate (P = 0.314) did not differ between trials. These data indicate that acute tyrosine administration did not influence self-paced endurance exercise performance in the heat. Plasma tyrosine availability is apparently not a key determinant of fatigue processes under these conditions.
Article
The efficacy of tyrosine, a catecholamine precursor, as a countermeasure in the reduction of cognitive decline during heat exposure (HE) using event-related potential P300, and contingent negative variation (CNV) was evaluated. Ten healthy males, age 20-30years participated in the study. Volunteers received placebo or tyrosine (6.5g) 90min prior to HE (1.5h in 45°C+30% RH). P300 latency was significantly increased (p<0.01) during exposure with placebo, which was reduced significantly (p<0.01) after tyrosine supplementation. There was an increase in CNV M100 latency (p<0.05) and reaction time (p<0.01) and decrease in M100 amplitude (p<0.01) during HE with placebo, which returns to near normal level with the tyrosine administration. A significantly higher plasma norepinephrine (p<0.05), dopamine and epinephrine levels were detected in tyrosine supplemented group post heat exposure. HE increases the brain catecholamine activity thereby reduces the plasma norepinephrine and dopamine level leading to a reduction in cognitive performances. Tyrosine supplementation increases the catecholamine level and reduces the impairment of cognitive performance during HE.
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Schizophrenia patients are behaviorally supersensitive to dopamine-like drugs such as amphetamine or methylphenidate, meaning that patients respond to such drugs with increased psychotic symptoms, as compared to control subjects. A basis of such supersensitivity may be an increased pre-synaptic release of dopamine or a post-synaptic elevation of D2 receptors or of D2High receptors in active stages of schizophrenia. While the pre-synaptic release of dopamine is normal in stable patients with schizophrenia, brain imaging studies find that D2 receptors are increased by an average of 5.8% in antipsychotic-free schizophrenia patients. It is possible that the behavioral supersensitivity may stem from more D2High receptors in schizophrenia. Although the antipsychotic/dopamine D2 receptor can exist in vitro in a state of high affinity for dopamine (as D2High), or in a state of low affinity for dopamine (as D2Low), there is no clear evidence that D2High states can be selectively labeled or stably exist in vivo. Nevertheless, two studies revealed an 80% increase in apparent D2High receptors in schizophrenia patients after reducing endogenous dopamine. The elevation in apparent D2High receptors in vivo in schizophrenia matches the elevation in D2High receptors in vitro in animal models of psychosis, including dopamine-supersensitive animals pretreated with amphetamine, marijuana, or phencyclidine, or animals with gene knockouts in various neurotransmitter pathways, including those for glutamate receptors. The elevation of D2High receptors in vitro and the increased apparent D2High receptors in vivo is consistent with behavioral dopamine supersensitivity in schizophrenia patients.
Article
Eight young men were recruited to a study designed to examine the effect of tyrosine (TYR) supplementation on the capacity to perform prolonged exercise in a warm environment. Subjects entered the laboratory in the morning and remained seated for 1 hr before cycling to exhaustion at 70% VO2peak. Two 250-ml aliquots of a placebo (PLA ) or a TYR solution were ingested at 30-min intervals before exercise, with an additional 150 ml consumed every 15 min throughout exercise (total TYR dose: 150 mg/kg BM). Cognitive function was assessed before drink ingestion, at the end of the rest period, and at exhaustion. TYR ingestion had no effect on exercise capacity (PLA 61.4 ± 13.7 min, TYR 60.2 ± 15.4 min; p = .505). No differences in heart rate (p = .380), core temperature (p = .554), or weighted mean skin temperature (p = .167) were apparent between trials. Ingestion of TYR produced a marked increase in serum TYR concentrations (+236 ± 46 μmol/L; p < .001), with this difference maintained throughout exercise. No change was apparent during the PLA trial (p = .924). Exercise caused an increase in error rate during the complex component of the Stroop test (p = .034), but this response was not influenced by the drink ingested. No other component of cognitive function was altered by the protocol (all p > .05). Ingestion of a TYR solution did not influence time to exhaustion or several aspects of cognitive function when exercise was undertaken in a warm environment.
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Tyrosine hydroxylation is considered to be the rate-limiting step in catecholamine synthesis. It is also assumed that under usual conditions, tyrosine 3-monooxygenase (EC 1.14.16.2) (tyrosine hydroxylase - TH) is close to full saturation with its l-tyrosine substrate and hence that raising the availability of l-tyrosine does not substantially increase 3,4-dihydroxyphenylalanine (DOPA) synthesis. We evaluated this in vivo by reverse dialysis of the aromatic-l-amino-acid decarboxylase (EC 4.1.1.28) inhibitor NSD-1015 (20μM) and selected concentrations of l- or d-tyrosine. In striatum, extracellular DOPA levels increased linearly (maximum 250% control) as l-tyrosine concentrations were raised from 0-1000μM. In medial prefrontal cortex, DOPA levels reached a maximum (300% control) at l-tyrosine 62.5-125μM but still remained significantly elevated (200% control) at higher l-tyrosine concentrations (250-500μM). At the l-tyrosine concentrations tested, DOPA levels were never below those of controls. d-tyrosine (62.5μM) did not affect DOPA levels. The degree to which the elevation of DOPA levels represents a net increase in tyrosine hydroxylation as opposed to heteroexchange of l-TYR for intracellular DOPA remains to be determined. However, one interpretation of the data is that under usual in vivo conditions brain TH may not be near full saturation with l-tyrosine and that mechanisms other than tyrosine hydroxylation may be more important in the acute regulation of brain catecholamine synthesis than previously appreciated. This would have implications for the pathophysiology and treatment of neuropsychiatric conditions in which dysregulation of DA transmission and l-tyrosine transport have been implicated.
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Tyrosine hydroxylase (TH) is the rate-limiting enzyme in brain catecholamine biosynthesis, and tetrahydrobiopterin is its cofactor. Research has focused on identifying mechanisms of TH activity regulation. TH activity is modulated by the cofactor itself, and is enhanced by several kinases phosphorylating key serines in the TH regulatory domain. Aside from these, the mechanisms that control TH gene transcription and TH mRNA translation are also related with the regulation of TH activity. Parkinson's disease (PD) is characterized by severe loss of dopaminergic neurons and depletion of dopamine in substantia nigra. Reduction of TH expression results in diminished dopamine synthesis and leads to PD; thus TH is essential in the pathogenesy of PD. It has also been shown that dysregulation of TH activity will contribute to PD. For example, α-synuclein represses TH not only by inhibiting phosphorylation at Ser40 of TH, but also by stimulating protein phosphatase 2A activity, which decreases dopamine synthesis and leads to parkinsonism. Based on these studies of TH in PD pathogenesis, a therapeutic strategy aimed to improve striatal TH expression in PD has received wide interest. Evidence shows that using drugs or other treatment methods such as gene replacement therapy to increase nigrostriatal TH expression is an effective therapy for PD. Further investigation of TH regulatory mechanisms will not only provide additional drug targets for PD, but may also help to identify new PD therapeutics.
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The effects of acute cold stress were assessed behaviorally and neurochemically. The norepinephrine (NE) precursor, tyrosine (TYR), the catecholamine-releasing compound, amphetamine (AMPH), and the adrenoceptor agonist, phenylpropanolamine (PPA), were administered systemically either alone or in conjunction with TYR 30 min prior to cold exposure. All three sympathomimetic treatments dose-dependently improved performance in a forced swim test following hypothermia (Tc=30°C). AMPH/TYR or PPA/TYR combinations further improved performance vs. either agent given alone. Microdialysis showed elevated hippocampal NE concentrations in response to hypothermia. TYR further elevated NE concentration in cold/restrained rats vs. saline (SAL)-treated controls. These results suggest that sympathomimetic agents, including the nutrient TYR, which enhance noradrenergic function, improve performance in animals acutely stressed by hypothermia.
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We treated 65 outpatients with RDC major depression in a randomized, prospective, double-blind comparison of oral L-tyrosine, 100 mg/kg/day, imipramine, 2.5 mg/kg/day, or placebo for 4 weeks. Tyrosine increased and imipramine decreased 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion significantly, but there was no evidence that tyrosine had antidepressant activity. The only side effect to achieve statistical significance was greater dry mouth with imipramine. MHPG excretion and plasma amino acid concentrations failed to predict or correlate with clinical improvement.
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Increasing dissatisfaction with the non-specificity of major depression has led many to propose more specific depressive subtyping models. The present meta-review seeks to map dominant depressive subtype models, and highlight definitions and overlaps. A database search in Medline and EMBASE of proposed depressive subtypes, and limited to reviews published between 2000 and 2011, was undertaken. Of the more than four thousand reviews, 754 were judged as potentially relevant and provided the base for the present selective meta-review. Fifteen subtype models were identified. The subtypes could be divided into five molar categories of (1) symptom-based subtypes, such as melancholia, psychotic depression, atypical depression and anxious depression, (2) aetiologically-based subtypes, exemplified by adjustment disorders, early trauma depression, reproductive depression, perinatal depression, organic depression and drug-induced depression, (3) time of onset-based subtypes, as illustrated by early and late onset depression, as well as seasonal affective disorder, (4) gender-based (e.g. female) depression, and (5) treatment resistant depression. An overview considering definition, bio-psycho-social correlates and the evidence base of treatment options for each subtype is provided. Despite the large data base, this meta-review is nevertheless narrative focused. Subtyping depression is a promising attempt to overcome the non-specificity of many diagnostic constructs such as major depression, both in relation to their intrinsic non-specificity and failure to provide treatment-specific information. If a subtyping model is to be advanced it would need, however, to demonstrate differential impacts of causes and treatments.