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Exercise and Brain Neurotransmission
Abstract
Physical exercise influences the central dopaminergic, noradrenergic and serotonergic systems. A number of studies have examined brain noradrenaline (norepinephrine), serotonin (5-hydroxytryptamine; 5-HT) and dopamine with exercise. Although there are great discrepancies in experimental protocols, the results indicate that there is evidence in favour of changes in synthesis and metabolism of monoamines during exercise. There is a possibility that the interactions between brain neurotransmitters and their specific receptors could play a role in the onset of fatigue during prolonged exercise. The data on the effects of branched chain amino acid (BCAA) supplementation and ‘central fatigue’ seem to be conflicting, although recent studies suggest that BCAA supplementation has no influence on endurance performance. There are numerous levels at which central neurotransmitters can affect motor behaviour; from sensory perception, and sensory-motor integration, to motor effector mechanisms. However, the crucial point is whether or not the changes in neurotransmitter levels trigger or reflect changes in monoamine release. Until recently most studies were done on homogenised tissue, which gives no indication of the dynamic release of neurotransmitters in the extracellular space of living organisms.
... Neurotransmitters are chemical messengers that transmit signals from neuron to synapses. Major neurotransmitters including NE, 5-HT, 5-HIAA, and DA are regulated by exercise and may affect brain function [28,29]. In general, upregulation of NE, 5-HT, 5-HIAA, and DA after drug administration is considered an anti-depressant effect. ...
... In general, upregulation of NE, 5-HT, 5-HIAA, and DA after drug administration is considered an anti-depressant effect. In vivo experiments have reported increased levels of NE, 5-HT, and DA in the brain and hypothalamus after various types of exercise [29,30]. Upregulation of these neurotransmitters is beneficial to the body, but excessive release of these neurotransmitters causes side effects such as muscle cramps [31]. ...
OBJECTIVES Jujubae fructus (JF, Ziziphus jujuba var. inermis Rehder) is an economically and agriculturally significant perennial fruit tree crop of the Rhamnaceae family and is used as a traditional herbal medicine. However, the anti-fatigue effect of JF has not been reported yet. The purpose of this study was to examine the anti-fatigue effect of JF by in vivo experiments.Methods Male ICR mice were classified into a saline-treated swimming load test group (control) and JF (1, 10, 100 mg/kg) supplied swimming load test group (JF), and randomly assigned to 5 mice per group. Distilled water and JF were orally administered. The anti-fatigue effect of JF was evaluated by open field test (OFT) and forced swimming test (FST).Results JF significantly increased the total distance moved in OFT in a dose-dependent manner. JF was significantly decreased immobility time compared to control group in the FST. The increase in lactic acid and lactate dehydrogenase after FST was suppressed by JF treatment. Consumption and recovery of energy sources (free fatty acid and triglyceride) were improved after FST through JF treatment. Administration of JF decreased the expression of neurotransmitters such as norepinephrine (NE), serotonin (5-HT), 5-hydroxyindole-acetic acid (5-HIAA), dopamine (DA) by FST in brain stem and hypothalamus.Conclusions Based on these results, this study provides scientific proof for anti-fatigue effect of JF and it could be a useful material.
... Higher intensity exercise can contribute to the exercise apathy [31]. Many people do not have positive experiences with exercise, since their physiological responses to exercise associated with neurotransmitters (e.g., dopamine, and serotonin associated with cortical reward centres) [32,33], endorphin or enkephalin (morphine-like hormones that inhibit pain and increase feelings of well-being) [34,35] release are muted compared to others who enjoy exercise. Hence, there is little or no reward of a runner's or exercise "high" (e.g., drug-induced euphoria) to provide exercise enjoyment and motivation to continue. ...
Background Findings from original research, systematic reviews, and meta-analyses have demonstrated the effectiveness of resistance training (RT) on markers of performance and health. However, the literature is inconsistent with regards to the dosage effects (frequency, intensity, time, type) of RT to maximize training-induced improvements. This is most likely due to moderating factors such as age, sex, and training status. Moreover, individuals with limited time to exercise or who lack motivation to perform RT are interested in the least amount of RT to improve physical fitness. Objectives The objective of this review was to investigate and identify lower than typically recommended RT dosages (i.e., shorter durations, lower volumes, and intensity activities) that can improve fitness components such as muscle strength and endurance for sedentary individuals or beginners not meeting the minimal recommendation of exercise. Methods Due to the broad research question involving different RT types, cohorts, and outcome measures (i.e., high het-erogeneity), a narrative review was selected instead of a systematic meta-analysis approach. Results It seems that one weekly RT session is sufficient to induce strength gains in RT beginners with < 3 sets and loads below 50% of one-repetition maximum (1RM). With regards to the number of repetitions, the literature is controversial and some authors report that repetition to failure is key to achieve optimal adaptations, while other authors report similar adaptations with fewer repetitions. Additionally, higher intensity or heavier loads tend to provide superior results. With regards to the RT type, multi-joint exercises induce similar or even larger effects than single-joint exercises. Conclusion The least amount of RT that can be performed to improve physical fitness for beginners for at least the first 12 weeks is one weekly session at intensities below 50% 1RM, with < 3 sets per multi-joint exercise.
... Higher intensity exercise can contribute to the exercise apathy [31]. Many people do not have positive experiences with exercise, since their physiological responses to exercise associated with neurotransmitters (e.g., dopamine, and serotonin associated with cortical reward centres) [32,33], endorphin or enkephalin (morphine-like hormones that inhibit pain and increase feelings of well-being) [34,35] release are muted compared to others who enjoy exercise. Hence, there is little or no reward of a runner's or exercise "high" (e.g., drug-induced euphoria) to provide exercise enjoyment and motivation to continue. ...
Background
Findings from original research, systematic reviews, and meta-analyses have demonstrated the effectiveness of resistance training (RT) on markers of performance and health. However, the literature is inconsistent with regards to the dosage effects (frequency, intensity, time, type) of RT to maximize training-induced improvements. This is most likely due to moderating factors such as age, sex, and training status. Moreover, individuals with limited time to exercise or who lack motivation to perform RT are interested in the least amount of RT to improve physical fitness.
Objectives
The objective of this review was to investigate and identify lower than typically recommended RT dosages (i.e., shorter durations, lower volumes, and intensity activities) that can improve fitness components such as muscle strength and endurance for sedentary individuals or beginners not meeting the minimal recommendation of exercise.
Methods
Due to the broad research question involving different RT types, cohorts, and outcome measures (i.e., high heterogeneity), a narrative review was selected instead of a systematic meta-analysis approach.
Results
It seems that one weekly RT session is sufficient to induce strength gains in RT beginners with < 3 sets and loads below 50% of one-repetition maximum (1RM). With regards to the number of repetitions, the literature is controversial and some authors report that repetition to failure is key to achieve optimal adaptations, while other authors report similar adaptations with fewer repetitions. Additionally, higher intensity or heavier loads tend to provide superior results. With regards to the RT type, multi-joint exercises induce similar or even larger effects than single-joint exercises.
Conclusion
The least amount of RT that can be performed to improve physical fitness for beginners for at least the first 12 weeks is one weekly session at intensities below 50% 1RM, with < 3 sets per multi-joint exercise.
... ; https://doi.org/10.1101/2023. 10.06.561205 doi: bioRxiv preprint accumulated in animal studies [2] using either ex vivo brain tissue assays with high-performance liquid chromatography/mass spectrometry [26,27], Western blot and immunofluorescence [28], and autoradiography [29]; or in vivo sampling with microdialysis [27,30,31]. In humans, in-vivo examinations have been conducted based on selective pharmacological manipulations to clarify the roles of dopaminergic [32][33][34][35][36], opioidergic [37,38], and endocannabinoid [38] neurotransmission in mediating exercise-induced affect modulation and rewardrelated behavior. ...
Dopaminergic, opiod and endocannabinoid neurotransmission are thought to play an important role in the neurobiology of acute exercise and, in particular, in mediating positive affective responses and reward processes. Recent evidence indicates that changes in fractional amplitude of low-frequency fluctuations (zfALFF) in resting-state functional MRI (rs-fMRI) may reflect changes in specific neurotransmitter systems as tested by means of spatial correlation analyses. Here, we tested for this relationship at different exercise intensities in twenty young healthy trained athletes performing low-intensity (LIIE), high-intensity (HIIE) interval exercises and a control condition on three separate days. Positive And Negative Affect Schedule (PANAS) scores and rs-fMRI were acquired before and after each of the three experimental conditions. Respective zfALFF changes were analysed using a repeated measures ANOVAs. We explored spatial cross-correlations between pre-to-post zfALFF changes in each condition with available neurotransmitter maps using the JuSpace toolbox, and performed additional analyses for the main systems of interest (dopaminergic, opiod, endocannabinoid), focusing on specific brain networks related to ‘reward’ and ‘emotion’. Elevated PANAS Positive Affect was observed after LIIE and HIIE but not in the control condition. HIIE compared to the control condition resulted in differential zfALFF decreases in precuneus, orbitofrontal cortex, thalamus, and cerebellum, whereas differential zfALFF increases were identified in hypothalamus, pituitary, and periaqueductal gray. The spatial alteration patterns in zfALFF were positively associated with dopaminergic and μ-opioidergic receptor distributions within the ‘reward’ network. These findings provide new insight into the neurobiology of exercise supporting the importance of reward-related neurotransmission during high-intensity physical activity.
Keypoints
Positive mood changes, indexed as elevated PANAS Positive Affect, were identified after high- and low-intensity exercise bouts, supporting previous accounts on mood-improving effects of physical activity.
High-intensity exercise was found to be associated with distributed changes in fractional amplitude of low-frequency fluctuations, indicating enduring neural activity changes after anaerobic exercise bouts.
Results of spatial cross-correlations with representative PET neurotransmitter distribution maps suggest involvement of endocannabinoid, dopaminergic, and opioidergic neurotransmission after high-intensity exercise.
Utilizing spatial cross-correlations of changes in fractional amplitude of low-frequency fluctuations and representative PET neurotransmitter distribution maps, despite being an indirect metric, provides an innovative methodological framework for human exercise research, as it allows for non-invasive testing of acute exercise-related changes multiple neurotransmitter.
... However, it seems widely agreed that exercise induces the release of various neurotransmitters from several neuromodulatory systems, including ascending projections to the PFC (Dietrich and Audiffren, 2011). Previous animal studies have indicated that an acute bout of exercise stimulated the release of acetylcholine from the nucleus basalis of Meynert (Kurosawa et al., 1993) and the release of dopamine in the nucleus accumbens (Meeusen and De Meirleir, 1995); moreover, an acute bout of exercise also enhanced the basal levels of noradrenaline in the locus coeruleus (Dishman et al., 1997). In addition, the catecholamine hypothesis demonstrated that acute exercise stimulated monoamine systems and enhanced the release of neurotransmitters such as noradrenaline and dopamine into brain regions, which provided a plausible explanation for the improvement of the cognitive process after acute exercise in adults (McMorris et al., 2008;McMorris, 2016McMorris, , 2021. ...
Introduction
Physical exercise not only benefits peoples’ health, but also improves their cognitive function. Although growing evidence suggests that high-intensity interval training (HIIT) is a time-efficient exercise regime that can improve inhibitory control performance by enhancing cortical activation in the prefrontal cortex, less is known about how Tabata training, a subset of HIIT that requires no equipment or facilities to perform, affects inhibitory control and cortical activation in young adults. Therefore, we aimed to reveal the effect of an acute bout of HIIT and Tabata training on inhibitory control and attempted to identify its potential neural substrates.
Methods
Forty-two young adults (mean age: 19.36 ± 1.36 years; 21 females) performed the Stroop task and Simon task before and after acute HIIT, Tabata training, or a control session, and cortical hemodynamic changes in the prefrontal area were monitored by functional near-infrared spectroscopy (fNIRS) during the tasks. Both HIIT and Tabata interventions lasted for a total of 12 min. The HIIT participants performed ergometer cycling at their 80% maximal aerobic power at 90–100 rpm, and the Tabata participants performed a total of 8 intense activities, such as jumping jacks, high knees, and butt kickers, without using equipment or facilities, keeping the heart rate at 80–95% of their maximum heart rate. Participants in the control group watched a sport video while sedentary. Cognitive tasks data and fNIRS data were analyzed by repeated-measures three-way ANOVA.
Results and discussion
Our results indicated that both the HIIT and Tabata groups exhibited reduced reaction times after the intervention, and there were alterations in activation patterns in the dorsolateral and ventrolateral prefrontal cortices.
... Put another way, exercising at and above ventilatory threshold is hypothesized to have a more pronounced effect on the emotional state of low-tolerant individuals when compared to their high-tolerant peers. Reaching ventilatory threshold can significantly increase the intensity of interoceptive sensory cues, force individuals to reassess the importance of the task at hand (da Costa et al., 2022), and even influence the dopaminergic system (Meeusen & De Meirleir, 1995). An inability to tolerate negative physical sensations during exercise is commonly accompanied by negative emotions (Timme & Brand, 2020), such as discouragement, overwhelm, and self-doubt. ...
The main objective of this study was to further understanding of the patterns of spectral connectivity during exercise in low- and high-tolerant individuals. Thirty-nine healthy individuals (i.e., 17 low- and 22 high-tolerant participants) took part in the present study. A state-of-the-art portable electroencephalography system was used to measure the brain's electrical activity during an incremental exercise test performed until the point of volitional exhaustion on a cycle ergometer. Spectral coherence was used to explore the patterns of connectivity in the frontal, central, and parietal regions of the brain. Physiological, perceptual, and affective responses were assessed throughout the exercise bout. The spontaneous eyeblink rate was also calculated prior to commencement and upon completion of the exercise trial as an indirect assessment of the dopaminergic system. The present findings indicate that high-tolerant individuals reported lower levels of perceived activation, especially during the preliminary stages of the exercise test. Participants in the high-tolerance group also reported greater levels of remembered pleasure upon completion of the exercise test. The data also revealed that high-tolerant individuals exhibited increased connectivity of theta waves between frontal, central, and parietal electrode sites and increased connectivity of beta waves, primarily within the parietal cortex. Correlational analysis indicated the possibility that low- and high-tolerant individuals make use of different neural networks to process and regulate their psychophysiological state during exercise-related situations. This strategy could potentially represent a conscious decision to downregulate affective arousal and facilitate the neural control of working muscles during situations of physical stress.
Throughout their lives, humans encounter a plethora of substances capable of inducing neurotoxic effects, including drugs, heavy metals and pesticides. Neurotoxicity manifests when exposure to these chemicals disrupts the normal functioning of the nervous system, and some neurotoxic agents have been linked to neurodegenerative pathologies such as Parkinson’s and Alzheimer’s disease. The growing concern surrounding the neurotoxic impacts of both naturally occurring and man-made toxic substances necessitates the identification of animal models for rapid testing across a wide spectrum of substances and concentrations, and the utilization of tools capable of detecting nervous system alterations spanning from the molecular level up to the behavioural one. Zebrafish ( Danio rerio ) is gaining prominence in the field of neuroscience due to its versatility. The possibility of analysing all developmental stages (embryo, larva and adult), applying the most common “omics” approaches (transcriptomics, proteomics, lipidomics, etc.) and conducting a wide range of behavioural tests makes zebrafish an excellent model for neurotoxicity studies. This review delves into the main experimental approaches adopted and the main markers analysed in neurotoxicity studies in zebrafish, showing that neurotoxic phenomena can be triggered not only by exposure to chemical substances but also by fluctuations in temperature. The findings presented here serve as a valuable resource for the study of neurotoxicity in zebrafish and define new scenarios in ecotoxicology suggesting that alterations in temperature can synergistically compound the neurotoxic effects of chemical substances, intensifying their detrimental impact on fish populations.
Neuroprotective and antiepileptogenic therapies have been extensively used for prevention and treatment of epilepsy. This chapter focuses on the positive influence of physical exercise observed in clinical studies and experimental models of epilepsy. We first give an overview of exercise in the healthy brain and in neurological diseases. We address the impact of previous exercise to reduce brain susceptibility to seizures after epilepsy has been established. Next, we explore the neurobiological mechanisms of these beneficial effects. Particular attention is given to the risks and benefits of physical exercise and possible seizure-precipitating factors related to exercise. Finally, this review provides evidence of exercise reducing comorbidities from epilepsy, improving the quality of life of people with epilepsy, and providing general guidance concerning participation in exercise/sport activities for people with epilepsy. Based on evidence from scientific literature, physical or sport activities represent an intervention that should be integrated as a complementary non-pharmacological treatment of epilepsy.KeywordsEpilepsySeizurePhysical exerciseQuality of lifeComplementary therapy
Objective:
This research explored the combined effects of transcranial direct current stimulation (tDCS) and aerobic exercise (AE) on executive function and specific serum biomarkers in healthy adults.
Methods:
Sixty adults were randomly assigned into tDCS+AE, tDCS only, or AE only groups. Interventions were carried out for 20 days. Executive functions were evaluated using tasks such as the 2,3-back task, the spatial working memory task, the Stroop test, T-test, and hexagonal obstacle jump task. Serum biomarkers, including brain-derived neurotrophic factor (BDNF), malondialdehyde (MDA), superoxide dismutase (SOD), glutamate, glutathione peroxidase 4 (GPX4) and iron ion, were analyzed pre- and post-intervention.
Results:
The tDCS+AE group showed superior enhancements in executive function, evidenced by improved accuracy rates in 2,3-back tasks, better performance in the staircase task, and reduced reaction times in the incongruent reaction time of the Stroop task compared to other groups. Importantly, we found substantial changes in serum biomarkers: increased levels of BDNF and SOD, and decreased levels of MDA and glutamate in the tDCS+AE group. These changes were significantly different when compared with the tDCS and AE only groups. Notably, these alterations in serum biomarkers were correlated with improvements in executive function tasks, thus offering a potential physiological basis for the cognitive improvements witnessed.
Conclusion:
The combined tDCS and AE intervention effectively improved executive function in healthy adults, with the improvements linked to changes in key serum biomarkers. The results emphasize the potential of combined tDCS and exercise interventions in engaging multiple physiological pathways to enhance cognitive function.
The nucleus accumbens (ACC) is a component of the ventral striatum and acts as a link between limbic and motor structures generating behavioral responses from limbic signals.1 Recent anatomical, pharmacological and electrophysiological data2’3 suggest that the nucleus accumbens can be divided into a core region, related to the caudate-putamen, and a shell region, associated with the limbic system. The objective of the present study is to investigate, in normal rats trained to run in a wheel-running device, the relationship between forced locomotion and spontaneous motor activity and dopaminergic transmission in core and shell areas. Changes in ascorbic acid (AA), dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) were recorded using in vivo differential normal pulse voltammetry (DNPV) with pretreated carbon fiber electrodes and numerical analysis of catechol peak.
This chapter discusses the comparison of three different in vivo models that estimate the release of neurotransmitters. The use of whole tissue neurochemical measurements for indices of in vivo release is described. In the chapter, the advantages and disadvantages of various in vivo release models are discussed and compared with the microdialysis technique. The brain tissue content of monoamine transmitters, such as dopamine, noradrenaline, and serotonin is relatively constant during treatment with drugs known to modify the release rate of these compounds. An indirect way to estimate drug-induced changes in the usage of dopamine and noradrenaline is the use of synthesis inhibitors. In general, antimuscarinic agents reduce the concentration of acetylcholine, whereas the muscarinic agonists increase the brain content of the transmitter. The muscarinic agonist oxotremorine decreases the dialysate content of acetylcholine, whereas the anticholinergic compound atropine increases the output of the transmitter. Neurotransmitters, such as acetylcholine and GABA are, after being released, metabolized to compounds that are reused for various biochemical purposes. Although not as sensitive as microdialysis, voltammetry is well suited to monitor the rapidly changing concentrations, such as the increase in extracellular dopamine induced by electrical stimulation and its rapid clearance by uptake mechanisms.
This chapter discusses the concept of intracerebral microdialysis. The idea of microdialysis is to mimic the passive function of a capillary blood vessel by perfusing a thin dialysis tube implanted into the tissue. Microdialysis is a technique for both recovering and administering substances in a tissue. The major features of microdialysis include: (1) it samples the extracellular fluid; (2) it can be performed locally in almost every organ and tissue of the body; (3) it can be performed in the intact tissue of the living, awake, and freely moving animal, distinguishing it from other preparations; and (4) it can be used for recovering and/or introducing endogenous and exogenous substances in the tissue. In essence, a microdialysis probe is a push-pull cannula with a dialysis membrane applied over its tip. Microdialysis has a real potential for studies in peripheral organs, including blood. Microdialysis is also finding its use in nonmammalians, such as the Lamprey and in plants. Microdialysis can easily bridge the gap between the animal model and man because of its simplicity and limited invasiveness. Microdialysis is becoming a promising tool in pharmacokinetic and drug distribution studies in animals as well as man.
: An investigation was made into the effects of running (I h at 20 m/min) on central serotonergic and dopaminergic metabolism in trained rats. Methodology involved continuous withdrawal of cerebrospinal fluid (CSF) from the third ventricle of conscious rats and measurements of tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels during a 2 h post-exercise period. All three compounds were increased during the hour following exercise and returned to their basal values within an hour later. CSF flow rate was stable when metabolite levels were elevated. Brain determinations indicated that CSF metabolite variations only qualitatively paralleled brain changes. Indeed, post-exercise TRP, 5-HIAA, and HVA levels were increased to a greater extent in brain when compared to CSF. It is suggested that increased serotonergic and dopaminergic metabolism, caused by motor activity, may be involved in the behavioral effects of exercise.
Long-term exercise is associated with an antidepressant effect in patients with mild to moderate forms of nonbipolar depression and appears to be a promising new approach to its treatment. Adaptive changes in serotonin (5-HT) receptor functioning appears to play an important role in mediating the action of various antidepressant treatments. We investigated the adaptive changes in behavioral sensitivity of the 5-HT receptor subtype following 4 weeks of swimming exercise in normal rats, as well as in an animal model of depression (3 week, variety of chronic stressors). 5-HT1A autoreceptor sensitivity was assessed by hyperphagic response induced by 8-OH-DPAT (0.25 mg/kg, IP); 5-HT1A postsynaptic receptor by 5-HT syndrome induced by 8-OH-DPAT (0.75 mg/kg, IP), and 5 Me-ODMT (5 mg/kg, IP); and 5-HT2 receptor by wet dog shakes response induced by quipazine (1 mg/kg, IP) and 5MeODMT (5 mg/kg, IP). It was observed that exercise training in normal rats resulted in enhanced sensitivity of the 5-HT2 receptors along with subsensitivity of 5-HT1A autoreceptors. Exercise, given prophylactically along with chronic stressors, was able to prevent the development of behavioral deficit in the open-field test, and the animals developed remarkably enhanced sensitivity of 5-HT2 receptors. This adaptive supersensitivity of 5-HT2 receptor is also seen after various antidepressant treatments and may play an important role in mediating the antidepressant action of exercise.