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Body weight of rats of different groups
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Widespread use of heavy metal lead (Pb) for various commercial purposes has resulted in the environmental contamination caused by this metal. The studies have shown a definite relationship between low level lead exposure during early brain development and deficit in children's cognitive functions. This study investigated the passive avoidance learn...
Contexts in source publication
Context 1
... was no significant difference between birth weight and weight gain in the lead exposed groups of rat pups (GL, L, G and PG), when compared to the normal control group (NC) on the day of birth, 7th, 14th and 21st postnatal day (Table 1). association between the properties of the chamber and the foot shock. ...Context 2
... the 2nd session, rats in all groups were able to reach the escape platform, much faster than during 1st session. In the sessions no. 3, 4, and 5, rats in all groups Abbreviations as in Table 1. Statistical significance of results (one way ANOVA, Bonferroni's test): * p < 0.05, ** p < 0.01, *** p < 0.001, when compared with NC; ...Context 3
... data represents mean ± standard deviation (M±SD) (N = 12 in each group). Abbreviations as in Table 1. Statistical significance of results (one way ANOVA, Bonferroni's test): * p < 0.05, ** p < 0.01, *** p < 0.001, when compared with NC, ### p < 0.001, when compared with PG, ## p < 0.001, when compared with G, # p < 0.01, when compared with L. Each data represents M±SD (N = 6 in each group). ...Citations
... The retention working memory of all rats was tested using the passive avoidance test (PAT) after DBS [6]. The retention memory of the rat is measured by its ability to remember a previously received electrical foot shock 24 h prior to the test. ...
To examine the effect of DBS of the lateral hypothalamic area (LHA) on age-related memory changes, neuronal firing from CA1, oxidative stress, and the expression of Hsp70, BDNF, and synaptophysin. 72 male rats were randomly allocated into 6 equal groups: a) normal young group (8 W), b) sham young group, c) DBS young group, d) normal old group (24 months), e) sham old group and f) DBS old group. Memory tests (passive avoidance and Y maze), oxidative stress markers (MDA, catalase, and GSH) and expression of Nrf2, HO-1, Hsp70, BDNF, and synaptophysin were measured by the end of the experiment. Also, in vivo recording of the neuronal firing of the CA1 region in the hippocampus was done. Old rats show significant decline in memories, antioxidant genes (Nrf2 and HO-1), antioxidants (GSH and catalase), Hsp70, BDNF, and synaptophysin with significant increase in MDA in hippocampus (p < 0.05) and DBS for LHA caused a significant improvement in memories in old rats, with significant rise in fast gamma and theta waves in CA1 region in old rats (p < 0.05). This was associated with a significant increase in antioxidants (GSH and CAT), antioxidant genes (Nrf2, HO-1), Hsp70, BDNF, and synaptophysin with significant reduction in MDA in hippocampus (p < 0.05). DBS for LHA ameliorates the age-induced memory decline. This might be due to increase in fast gamma in CA1, attenuation of oxidative stress, upregulation of Nrf2, HO-1, Hsp70, BDNF, and synaptophysin in the hippocampus.
Graphical Abstract
The effect of DBS of LHA on memory decline in aged rats. The process of aging results in degeneration of the hippocampus (critical region for memory and learning) via increasing the production of ROS which results in downregulation of Nrf2, HO1, Hsp70, BDNF and synaptophysin leading neuronal aggregates, degeneration and memory decline. On the other hand, DBS of LHA by high frequent currents survive the neurons of hippocampus via reduction of ROS production and upregulation of antioxidant genes (Nrf2/HO1), BDNF, synaptophysin and Hsp70 leading to improvement of memory decline. DBS = deep brain stimulation, LHA = lateral hypothalamic area, ROS = reactive oxygen species, Nrf2 = nuclear erythroid related factor, HO-1 = heme oxygenase-1, BDNF = brain derived neurotrophic factor, Hsp70 = heat shock protein 70. ↑ = increase, ↓ = decrease. Red arrows indicate the process of aging, while blue arrows indicate the process of DBS.
... The time (in seconds) until the first complete entry into the dim light chamber with all four paws was taken as "the step-through latency." The total time allowed for exploration of both partitions was 180 s (3 min), and the percent of time (in seconds) spent in each of the bright and dim light chambers was calculated (Rao Barkur & Bairy, 2015). ...
Haloperidol decanoate (HD) has been implicated in cognitive impairment. Agomelatine (AGO) has been claimed to improve cognition. We aimed at investigating the effects of HD + low- or high-dose AGO on cognition, verifying the melatonergic/dopaminergic to the cholinergic hypothesis of cognition and exploring relevant cardiovascular issues in adult male Wistar albino rats. HD + high-dose AGO prolonged the step-through latency by +61.47% (P < 0.0001), increased the time spent in bright light by +439.49% (P < 0.0001), reduced the time spent in dim light by -66.25% (P < 0.0001), and increased the percent of alternations by +71.25% (P < 0.0001), despite the reductions in brain acetylcholine level by -10.67% (P < 0.0001). Neurodegeneration was minimal, while the mean power frequency of the source wave was reduced by -23.39% (P < 0.05). Concurrently, the relative expression of brain melatonin type 2 receptors was reduced by -18.75% (P < 0.05), against increased expressions of dopamine type 5 receptors by +22.22% (P < 0.0001) and angiopoietin-like 4 by +119.18% (P < 0.0001). Meanwhile, electrocardiogram (ECG) demonstrated inverted P wave, reduced P wave duration by -36.15% (P < 0.0001) and PR interval by -19.91% (P < 0.0001), prolonged RR interval by +27.97% (P < 0.05), increased R wave amplitude by +523.15% (P < 0.0001), and a depressed ST segment and inverted T wave. In rats administered AGO, HD, or HD+ low-dose AGO, Alzheimer's disease (AD)-like neuropathologic features were more evident, accompanied by extensive ECG and neurochemical alterations. HD + high-dose AGO enhances cognition but alters cardiac electrophysiology. SIGNIFICANCE STATEMENT: Given the issue of cognitive impairment associated with HD and the claimed cognitive-enhancing activity of AGO, combined high-dose AGO with HD improved cognition of adult male rats, who exhibited minimal neurodegenerative changes. HD+ high-dose AGO was relatively safe regarding triggering epileptogenesis, while it altered cardiac electrophysiology. In the presence of low acetylcholine, the melatonergic/dopaminergic hypothesis, added to angiopoietin-like 4 and Krüppel-like factor 9, could offer some clue, thus offering novel targets for pharmacologic manipulation of cognition.
... After the mice entered the dark compartment, a second electric shock was administered. Mice were once more placed in the lit compartment after another hour in order to assess the step-through latency maximum of 300 s [5]. Compared to longer latency intervals, shorter latency durations signify poor memory recall. ...
The synaptic strength, which is crucial for memory and cognition function, is significantly influenced by sleep. According to earlier research, sound sleep is crucial for promoting connections between neural networks that are necessary for memory consolidation in the hippocampus. On the other hand, sleep deprivation can seriously impair the plasticity of our synapses. Sleep deprivation will disrupt LTP in region CA1 of the hippocampus, causing damage to neural connections. LTP has been proven to improve the connection between synapses, which will promote synaptic plasticity and so influence cognition function favorably. We also take a deeper look at LTP from a cellular and genetic perspective. In this review, we explore the detrimental effects of sleep deprivation on LTP stimulation and how they weaken synaptic plasticity and impair memory and learning performance. By studying LTP we can unravel the mysteries of brain function and the ability to learn and memory, and it can also give implications for understanding neurological disorders and advancing our knowledge of neurol system.
... The time to step into the dark compartment was recorded as post-shock latency in seconds. 22 ...
Background and aim
Activating NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is crucial in the pathogenesis of Alzheimer's disease (AD). A multimodal treatment intervention is the most feasible way to alter the course of AD progression. Hence, the current study was conducted to study the combination of betanin (BET) and virgin coconut oil (VCO) on NLRP3 regulation in aluminum chloride-induced AD in Wistar rats.
Experimental procedure
BET (100,200 mg/kg) and VCO (1, 5 g/kg) alone and in combination (BET 100 mg/kg + VCO 1 g/kg and BET 200 mg/kg + VCO 5 g/kg) were given orally for 42 days. On day 21 and 42nd, the behavioral test was performed to check the animal's cognition. Acetylcholinesterase (AChE) activity, oxidative stress markers, estimation of NLRP3 and IL-1β, and histological examinations were conducted in the hippocampus (H) and cortex (C).
Results and conclusion
Treatment with BET and VCO alone or combined improved behavioral characteristics (MWM and PA p < 0.0001; EPM p = 0.5184), inhibited AChE activity (C, p = 0.0101; H, p < 0.0001), and lowered oxidative stress in the brain. Also, combination treatment restored the levels of NLRP3 (C, p = 0.0062; H, p < 0.0001) and IL1β (C, p = 0.0005; H, p = 0.0098). The combination treatment significantly reduced the degree of neuronal degeneration, amyloid deposition, and necrosis in the brain tissue. The current study revealed that the combination strategy effectively controlled neuroinflammation via modulation of the NLRP3 inflammasome pathway, paving the way for the new treatment.
... Despite the effects of prenatal and/or postnatal lead exposure on later rodent offspring behavior being sometimes inconsistent, studies report it results in higher anxiety (Moreira et al., 2001), hyperaggression (Delville, 1999;Dolinsky et al., 1983;Kasten-Jolly et al., 2012), abnormal active (Rodrigues et al., 1996) and passive (Barkur & Bairy, 2015; Barrett & Livesey, 1983) avoidance, hyperactivity (Ma et al., 1999;Rodrigues et al., 1996), impaired learning and memory (Barkur & Bairy, 2015;Ramirez Ortega et al., 2020;Yang et al., 2003;Zenick et al., 1978), and altered sociosexual behavior (McGivern et al., 1991;Sant'Ana et al., 2001). Research also points to profound changes in reward encoding and reactivity, including impaired operant responding for reward (Angell & Weiss, 1982) and enhanced sensitivity to reward omission (Beaudin et al., 2007). ...
... Despite the effects of prenatal and/or postnatal lead exposure on later rodent offspring behavior being sometimes inconsistent, studies report it results in higher anxiety (Moreira et al., 2001), hyperaggression (Delville, 1999;Dolinsky et al., 1983;Kasten-Jolly et al., 2012), abnormal active (Rodrigues et al., 1996) and passive (Barkur & Bairy, 2015; Barrett & Livesey, 1983) avoidance, hyperactivity (Ma et al., 1999;Rodrigues et al., 1996), impaired learning and memory (Barkur & Bairy, 2015;Ramirez Ortega et al., 2020;Yang et al., 2003;Zenick et al., 1978), and altered sociosexual behavior (McGivern et al., 1991;Sant'Ana et al., 2001). Research also points to profound changes in reward encoding and reactivity, including impaired operant responding for reward (Angell & Weiss, 1982) and enhanced sensitivity to reward omission (Beaudin et al., 2007). ...
Despite early‐life disadvantage (ELD) in humans being a highly heterogenous construct, it consistently predicts negative neurobehavioral outcomes. The numerous environmental contributors and neural mechanisms underlying ELD remain unclear, though. We used a laboratory rat model to evaluate the effects of limited resources and/or heavy metal exposure on mothers and their adult male and female offspring. Dams and litters were chronically exposed to restricted (1‐cm deep) or ample (4‐cm deep) home cage bedding postpartum, with or without lead acetate (0.1%) in their drinking water from insemination through 1‐week postweaning. Restricted‐bedding mothers showed more pup‐directed behaviors and behavioral fragmentation, while lead‐exposed mothers showed more nestbuilding. Restricted bedding‐raised male offspring showed higher anxiety and aggression. Either restricted bedding or lead exposure impaired goal‐directed performance in a reinforcer devaluation task in females, whereas restricted bedding alone disrupted it in males. Lead exposure, but not limited bedding, also reduced sucrose reward sensitivity in a progressive ratio task in females. D1 and D2 receptor mRNA in the medial prefrontal cortex and nucleus accumbens (NAc) were each affected by the early‐life treatments and differently between the sexes. Most notably, adult males (but not females) exposed to both early‐life treatments had greatly increased D1 receptor mRNA in the NAc core. These results illuminate neural mechanisms through which ELD threatens neurobehavioral development and highlight forebrain dopamine as a factor.
... The passive avoidance (PA) test determines the ability of an animal to assess memory retention deficit [44]. The device consisted of two compartments (25 × 25 × 25 cm): one was brightly illuminated, whereas the other one was dark. ...
Recent evidences indicate that there is a substantial increase in worldwide cases of dementia. Alzheimer’s disease is the leading cause of dementia and may contribute to 60–70% of cases. Quercetin is a unique bioflavonoid that has numerous therapeutic benefits such as anti-allergy, anti-ulcer, anti-inflammatory, anti-hypertensive, anti-cancer, immuno-modulatory, anti-infective, antioxidant, acetylcholinesterase inhibitory activity, neuroprotective effects, etc. In the present study, we evaluated the neuroprotective effect of orally administered quercetin with memantine in albino Wistar rats after inducing neurotoxicity through AlCl3 (100 mg/kg, p.o.). Chronic administration of AlCl3 resulted in poor retention of memory and significant oxidative damage. Various behavioral parameters, such as locomotor activity, Morris water maze, elevated plus maze, and passive avoidance test, were assessed on days 21 and 42 of the study. The animals were euthanatized following the completion of the last behavioral assessment. Various oxidative stress parameters were assessed to know the extent of oxidative damage to brain tissue. Quercetin with memantine has shown significant improvement in behavioral studies, inhibition of AChE activity, and reduction in oxidative stress parameters. Histopathological studies assessed for cortex and hippocampus using hematoxylin and eosin (H&E), and Congo red stain demonstrated a reduction in amyloid-β plaque formation after treatment of quercetin with memantine. Immunohistochemistry showed that quercetin with memantine treatment also improved the expression of brain-derived neurotrophic factor (BDNF) and inhibited amyloid-β plaque formation. The present study results demonstrated protective effects of treatment of quercetin with memantine in the neurotoxicity linked to aluminum chloride in albino Wistar rats.
... Juvenile lead exposure causes cognitive dysfunction in adult rats [39]. Some studies have also found that prenatal lead exposure in mothers can cause neurological damage to the offspring [40]. In the current study, we found interestingly that in the Morris water maze test, female mice exposed to lead during the perinatal period had a decrease in the spatial memory of their offspring. ...
It is well known that SLC30A10 and RAGE play a crucial role in regulating the transport and accumulation of Aβ plaques. Our previous studies have shown that early exposure to lead can cause cerebral damage to pups due to the accumulation of Aβ and the deposition of amyloid plaques. However, the effect of lead on the protein expression levels of SLC30A10 and RAGE remains unclear. This study aimed to verify that maternal exposure to lead-containing drinking water during pregnancy would affect the expression of SLC30A10 and RAGE proteins in mice offspring, further verifying the lead-induced neurotoxicity. Four groups of mice were exposed to 0 mM, 0.25 mM, 0.5 mM, and 1 mM of lead for 42 consecutive days from pregnancy to weaning, and the offspring mice were tested on postnatal day 21. The levels of lead in the blood, hippocampus, and cerebral cortex were examined; the learning and memory abilities of the mice were investigated using the Morris water maze; the expression levels of SLC30A10 and RAGE in the hippocampus and cerebral cortex were examined using Western blotting and immunofluorescence. The results showed that the lead concentration in the brain and blood of the mice increased along with the lead content of the mothers during the lead exposure period ( P < 0.05). In the Morris water maze test, the spatial memory of the lead exposure group was lower than that of the control group ( P < 0.05). Both Immunofluorescence and Western blot analysis showed that the hippocampal and cerebral cortex of the offspring were proportionally affected by differential levels of lead exposure. The expression levels of SLC30A10 were negatively correlated with lead doses ( P < 0.05). Surprisingly, under the same conditions, the expression of RAGE in the hippocampus and cortex of offspring was positively correlated with lead doses ( P < 0.05). SLC30A10 may play a differential role in aggravated Aβ accumulation and transportation compared with RAGE. A difference in RAGE and SLC30A10 expression in the brain could contribute to lead-induced neurotoxicity.
... Histopathological examination of cresyl violet-stained hippocampal slices of aluminium chloride group in present study have shown presence of pyknotic cells, densely stained pyramidal cells with irregular morphology with cellular dispersions and loss of cell bodies with their Nissl's substance connoting neuronal degeneration. Earlier studies have reported similar morphological irregularities in pyramidal cells with aluminium chloride exposure 35,[48][49][50] . A significant decline in pyramidal cell count in CA3 region of the hippocampus has been observed in aluminium chloride group in this study. ...
Introduction: Type 2 diabetes is considered a pivotal risk factor for Alzheimer’s disease (AD). Aluminium chloride induces hippocampal structural & functional abnormality and causes neurodegeneration. Our study evaluated the effects of vildagliptin on spatial memory, cholinergic activity, and neuronal survival in cornu ammonis 3 (CA3) region of hippocampus in an aluminium chloride-induced AD in male Wistar rats. Materials and method: Male Wistar rats were randomly divided into five groups. All animals except normal control were exposed to aluminium chloride (17 mg/kg/day) and group 3, 4 and 5 were simultaneously received rivastigmine (6 mg/kg/day), vildagliptin (5 mg/kg/day and 10 mg/kg/day) treatment respectively for 30 days. Assessment of spatial memory was followed by estimation of acetylcholinesterase (AChE) activity and quantification of neuronal cell count in CA3 region of hippocampus. Results: Vildagliptin improved spatial memory, decreased acetylcholinesterase levels, and improved neuronal count in CA3 region of hippocampus through multimodal approach. Conclusion: Vildagliptin treatment significantly attenuated aluminium chloride-induced cognitive deficits. It may serve as a promising candidate in the management of concomitant AD and type 2 diabetes mellitus (T2DM).
... After 24 h, retention test was conducted where animals were placed in the illuminated compartment and total time spent in the dark chamber was recorded. (Barkur and Bairy 2015). ...
Diosgenin is a neurosteroid derived from the plants and has been previously reported for its numerous health beneficial properties, such as anti-arrhythmic, hypolipidemic, and antiproliferative effects. Although several studies conducted earlier suggested cognition enhancement actions of diosgenin against neurodegenerative disorders, but the molecular mechanisms underlying are not clearly understood. In the present study, we investigated the neuroprotective effect of diosgenin in the Wistar rats that received an intracerebroventricular injection of Amyloid-β (1–42) peptides, representing a rodent model of Alzheimer’s disease (AD). Animals were treated with 100 and 200 mg/kg/p.o of diosgenin for 28 days, followed by Amyloid-β (1–42) peptides infusion. Animals were assessed for the spatial learning and memory by using radial arm maze and passive avoidance task. Subsequently, animals were euthanized and brains were collected for biochemical estimations and histopathological studies. Our results revealed that, diosgenin administration dose dependently improved the spatial learning and memory and protected the animals from Amyloid-β (1–42) peptides induced disrupted cognitive functions. Further, biochemical analysis showed that diosgenin successfully attenuated Amyloid-β (1–42) mediated plaque load, oxidative stress, neuroinflammation and elevated acetylcholinesterase activity. In addition, histopathological evaluation also supported neuroprotective effects of diosgenin in hippocampus of rat brain when assessed using hematoxylin–eosin and Cresyl Violet staining. Thus, the aforementioned effects suggested protective action of diosgenin against Aβ (1–42) induced neuronal damage and thereby can serve as a potential therapeutic candidate for AD.
... The different concentration of lead acetate was administered through drinking water. This is based on the method used by [15], which resulted in causing lead poisoning in the rat pups. ...
Objectives: The objective of this study was to find the histologic and motor activity effect of lead on prenatally and postnatally exposed Wistar rats. Methods: In this study, twelve Wistar Rats were used and grouped into four groups of two females and one male. Group I rats served as the control and allowed feed and water freely. The rats in Group II were administered 500ppm of Pb through drinking water from gestation day 8 (GD8) to parturition (GD21). While Group III rats were given 500ppm of Pb in drinking water from postnatal day 1 (PND1) to PND21. The rats in the fourth group (Group IV) were given 500ppm of Pb from GD8 to PND21. Palmer grasp reflex was conducted to assess the motor activity of the rat pups. The animals were then humanely sacrificed and the frontal cortices were isolated for routine histological processing. Results: The histological study has shown normal neurons in the control group while degenerating cells exhibiting karyolysis, pyknosis, karyorrhexis, vacuolation were seen in the lead-treated groups. Group II and Group IV showed considerate deficit in their motor activity while Group III showed mild effect. Conclusion: From this study, lead exposure of Wistar rats at both prenatal and postnatal period of development has effect on the histology of the frontal cortex as well as on their motor activity.
