Reduced Acetylcholinesterase Activity Research Articles

Ameliorative effect of walnut oil against cognitive impairment in Alzheimers type dementia in rodent

Walnut oil (WO), known for abundant polyunsaturated fatty acids and an array of bioactive substances such as tocopherols, phytosterols, squalene, melatonin, and polyphenols, which is endowed with numerous health advantages. The primary objective of this research was to ascertain the impact of WO on cognitive deficits in learning and memory impairment mice caused by scopolamine (SCOP). The Morris water maze and the step-down avoidance test were utilized to assess the memory and learning capabilities. WO notably counteracted the detrimental effects of SCOP on learning and memory in the Morris water maze, as indicated by a reduction in escape latency and swimming distance. Likewise, WO administration led to a notably reduced number of errors in training trial and an increased latency in testing trial when compared to the SCOP group in the step-down avoidance test,. Moreover, WO activated the cholinergic system of the brain by upregulating choline acetyltransferase activity and reducing acetylcholinesterase activity. These results suggest that WO has the potential to protect against memory decline in mice, offering a promising strategy for the prevention of memory-related disorders.

Chemical analysis of Alliin-Rich Allium sativum (Garlic) extract and its safety evaluation in Drosophila melanogaster

Garlic (Allium sativum) has been traditionally valued for its medicinal properties attributed to the presence of organosulfur compounds. Despite its benefits, concerns about herbal extract toxicity have arisen, necessitating safety assessment. This study was designed to evaluate the chemical analysis and safety profile of Alliin-Rich Garlic Extract (ARGE) using Drosophila melanogaster as a model organism. The ARGE was extracted from garlic cloves (Allium sativum Linn: UIH-23262) using a microwave-assisted method and characterized using UPLC-ESI-MS, 1H NMR, HPLC and IR. Its safety evaluation was determined using D. melanogaster (Harwich strain), and various assays were conducted on 1–3-day-old flies. Toxicological markers and oxidative stress were assessed to understand the impact of ARGE on the flies. Chemical profiling of ARGE using UPLC-ESI-MS, confirmed the presence of alliin (S-ally-L-cysteine-S-oxide), L-arginine, γ-glutamylmethionine, S-(2-carboxypropyl) glutathione, N-γ-glutamyl-S-(1-propenyl) cysteine, N-γ-glutamyl-S-(2-propenyl) cysteine, N-γ-glutamylphenylalanine, S-(allylthio) cysteine, γ-glutamyl-S-allylthiocysteine and eruboside B. HPLC confirmed an alliin content of 0.073 mg/g. Toxicological assessment in D. melanogaster revealed that ARGE enhanced antioxidant defenses by increasing total thiol levels and GST activity, while reducing acetylcholinesterase activity. No significant alteration was observed in catalase activity and cellular metabolic rate. Histological examination revealed no alterations in the histoarchitecture of the brain, fat body or gut of D. melanogaster. The study demonstrated the safety of ARGE in D. melanogaster, supporting its potential as a safe herbal remedy.

Assessment of Neurotoxic Mechanisms of Individual and Binary Mixtures of Cobalt, Nickel and Lead in Hippocampal Neuronal Cells.

Many studies have focused on the neurotoxic effects of single metals, while investigation on the exposure to metal mixtures, which mainly occur in real-life situations, is scarce. This study sought to assess the neurotoxic effect of Ni, Co, and Pb binary mixtures and their individual effects in hippocampal neuronal cells (HT-22). Cells were exposed to Ni, Co, and Pb separately for 48 h at 37°C and 5% CO2, and cell viability was assessed. Morphological assessment of the cells exposed to binary mixtures of Co, Ni, and Pb and single metals was assessed using a microscope. Furthermore, acetylcholinesterase (AChE) activity, oxidative stress biomarkers (glutathione [GSH] and malondialdehyde [MDA] levels, catalase [CAT], and glutathione-S transferase [GST] activities) and nitric oxide [NO] levels were evaluated after treatment with the binary mixtures and single metals. Binary mixtures of the metals reduced cell viability, exerting an additivity action. The combinations also exerted synergistic action, as revealed by the combination index. Furthermore, a significant reduction in AChE activity, GSH levels, CAT and GST activities, and high MDA and NO levels were observed in neuronal cells. The additive interactions and synergistic actions of the binary mixtures might contribute to the significant reduction of AChE activity, GSH levels, GST, and CAT activities, and an increase in MDA and NO levels. The findings from this study revealed significant evidence that binary mixtures of Co, Pb, and Ni may induce impaired neuronal function and, ultimately, neurodegeneration.

Enhancement of Cognitive Function by Andrographolide-Loaded Lactose β-Cyclodextrin Nanoparticles: Synthesis, Optimization, and Behavioural Assessment.

This study investigates whether Andrographolide-loaded Lactose β-Cyclodextrin (ALN-βCD) nanoparticles enhance cognitive function, particularly spatial learning and memory. The successful conjugation of lactose to β-cyclodextrin was confirmed via 1H NMR spectroscopy, facilitating neuronal cell entry. The solvent evaporation method was used to create the nanoparticles, which were characterised for particle size, PDI, zeta potential, and drug release. The nanoparticles exhibited a size of 247.9 ± 3.2 nm, a PDI of 0.5 ± 0.02, and a zeta potential of 26.8 ± 2.5 mV. FTIR and TEM analyses, along with in vitro drug release and BBB permeability studies, confirmed their stability and efficacy. Behavioural tests, including the Elevated Plus Maze, Y-Maze, Object Recognition, and Locomotor Activity tests, demonstrated significant improvements in memory, motor coordination, and exploration time in the nanoparticle-treated groups. The group treated with ALN-βCD at a dose of 100 mg/kg/p.o. showed superior cognitive performance compared to the group receiving free andrographolides (AG). Biochemical assays indicated a significant reduction in acetylcholinesterase activity and lipid peroxidation, suggesting increased acetylcholine levels and reduced oxidative stress. Histopathological examination showed improved neuronal function without toxicity. The results showed significant improvements (p < 0.001) in memory and cognitive abilities in experimental animals, highlighting the potential of ALN-βCD nanoparticles as a non-invasive treatment for memory loss. These promising findings warrant further exploration through clinical trials.

Marrubium vulgare Extract Improves Spatial Working Memory and Oxidative Stress Damage in Scopolamine-Treated Rats.

The cholinergic neuronal loss in the basal forebrain and increasing brain oxidative stress are one of the main features of the brain suffering from Alzheimer's disease. Marrubium vulgare (M. vulgare), commonly known as 'white horehound,' possesses a variety of valuable properties, such as antioxidative, anti-inflammatory, and antidiabetic activities. Moreover, it possesses neuromodulatory properties that could potentially impact short-term memory functions. The present study was undertaken to investigate the preventive effects of water M. vulgare extract on working memory, cholinergic neurotransmission, and oxidative stress in rats with scopolamine (Sco)-induced dementia. Male Wistar rats (200-250 g) were divided into four experimental groups. The plant extract was administered orally for 21 days, and Sco (2 mg/kg) was administered intraperitoneally for 11 consecutive days. The behavioral performance of the animals was evaluated by the T-maze test. The effect of the extract on acetylcholinesterase (AChE) activity and antioxidant status in cortex and hippocampus were also monitored. Our experimental data revealed that treatment with M. vulgare significantly increased the percentage of correct choices of rats with Sco-induced dementia in the T maze test (by 38%, p < 0.05). Additionally, it reduced AChE activity in the hippocampus (by 20%, p < 0.05) and alleviated oxidative stress induced by Sco, particularly in the cortex. M. vulgare water extract demonstrated working memory preserving effect in rats with Sco-induced dementia, AChE inhibitory activity and in vivo antioxidant potential, and deserve further attention.

Effects of Green and Gold Kiwifruit Varieties on Antioxidant Neuroprotective Potential in Pigs as a Model for Human Adults.

Kiwifruit (KF) has shown neuroprotective potential in cell-based and rodent models by augmenting the capacity of endogenous antioxidant systems. This study aimed to determine whether KF consumption modulates the antioxidant capacity of plasma and brain tissue in growing pigs. Eighteen male pigs were divided equally into three groups: (1) bread, (2) bread + Actinidia deliciosa cv. 'Hayward' (green-fleshed), and (3) bread + A. chinensis cv. 'Hort16A' (yellow-fleshed). Following consumption of the diets for eight days, plasma and brain tissue (brain stem, corpus striatum, hippocampus, and prefrontal cortex) were collected and measured for biomarkers of antioxidant capacity, enzyme activity, and protein expression assessments. Green KF significantly increased ferric-reducing antioxidant potential (FRAP) in plasma and all brain regions compared with the bread-only diet. Gold KF increased plasma ascorbate concentration and trended towards reducing acetylcholinesterase activity in the brain compared with the bread-only diet. Pearson correlation analysis revealed a significant positive correlation between FRAP in the brain stem, prefrontal cortex, and hippocampus with the total polyphenol concentration of dietary interventions. These findings provide exploratory evidence for the benefits of KF constituents in augmenting the brain's antioxidant capacity that may support neurological homeostasis during oxidative stress.

The protective effect of Astaxanthin on scopolamine - induced Alzheimer's model in mice.

To investigate the fundamental mechanisms of the neuroprotective impact of Astaxanthin (AST) in a mouse model of Alzheimer's disease (AD) induced by scopolamine. This research constituted an in vivo animal study encompassing 36 adult male mice, divided into 6 groups: Control, 100mg/kg AST, 2mg/kg scopolamine (AD group), 100mg/kg AST+2mg/kg scopolamine, 3mg/kg galantamine+2mg/kg scopolamine, and 100mg/kg AST+3mg/kg galantamine+2mg/kg scopolamine. After 14 days, the mice's short-term memory, hippocampus tissue, oxidative and inflammatory markers were evaluated. The AST demonstrated a beneficial influence on short-term memory and a reduction in acetylcholinesterase activity in the brain. It exhibited neuroprotective and anti-amyloidogenic properties, significantly decreased pro-inflammatory markers and oxidative stress, and reversed the decline of the Akt-1 and phosphorylated Akt pathway, a crucial regulator of abnormal tau. Furthermore, AST enhanced the effect of galantamine in reducing inflammation and oxidative stress. The findings indicate that AST may offer therapeutic benefits against cognitive dysfunction in AD. This is attributed to its ability to reduce oxidative stress, control neuroinflammation, and enhance Akt-1 and pAkt levels, thereby underscoring its potential in AD treatment strategies.

Rhodamine B, an organic environmental pollutant induces reproductive toxicity in parental and teratogenicity in F1 generation in vivo

This study investigated the reproductive toxicity of rhodamine B in zebrafish and its transgenerational effects on the F1 generation. In silico toxicity predictions revealed high toxicity of rhodamine B, mainly targeting pathways associated with the reproductive and endocrine systems. In vivo experiments on zebrafish demonstrated that rhodamine B exposure at a concentration of 1.5 mg/L led to significant impairments in fecundity parameters, particularly affecting females. Histopathological analysis revealed distinct changes in reproductive organs, further confirming the reproductive toxicity of rhodamine B, with females being more susceptible than males. Gene expression studies indicated significant suppression of genes crucial for ovulation in rhodamine B-treated female fish, highlighting hormonal imbalance as a potential mechanism of reproductive toxicity. Furthermore, bioaccumulation studies showed the presence of rhodamine B in both adult fish gonads and F1 generation samples, suggesting transgenerational transfer of the dye. Embryotoxicity studies on F1 generation larvae demonstrated reduced survival rates, lower hatching rates, and increased malformations in groups exposed to rhodamine B. Moreover, rhodamine B induced oxidative stress in F1 generation larvae, as evidenced by elevated levels of reactive oxygen species and altered antioxidant enzyme activity. Neurotoxicity assessments revealed reduced acetylcholinesterase activity, indicating potential neurological impairments in F1 generation larvae. Additionally, locomotory defects and skeletal abnormalities were observed in F1 generation larvae exposed to rhodamine B. This study provides comprehensive evidence of the reproductive toxicity of rhodamine B in adult zebrafish and its transgenerational effects on the F1 generation.

Alcohol and Caffeine Co-Administration Increased Acetylcholinesterase Activity and Inflammatory Cytokines in Sleep-Deprived Rats: Implications for Cognitive Decline and Depressive-Like Manifestations.

Sleep deprivation is a major health problem in modern society; it has been worsened by alcohol and caffeine intake to stay awake and improve bodily activities, an experience common among night-shift workers. For the present study, 50 adult male Wistar rats weighing between 150 g and 200 g were randomly selected and divided into 5 groups of 10 rats each (n = 10). Group 1 was the control group; group 2 was the group of sleep-deprived (SD) rats; group 3 was composed SD rats submitted to the administration of 20% alcohol; group 4 comprised SD rats submitted to the administration of 200 mg/kg of caffeine; and Group 5 was composed of SD rats who underwent the co-administration of 20% alcohol and 200 mg/kg of caffeine. At the end of 28 days, the animals were euthanized, and blood samples were collected for biochemical analysis. Memory, anxiety, social behavior and locomotive activity were assessed using the Y-maze, the elevated plus maze, the hole-board and three-chambered social approach tests, and the open field test. The plasma levels of the acetylcholinesterase (AChE) enzyme and inflammatory cytokines (interleukin 6 [IL-6], interleukin 10 [IL-10], and tumor necrosis factor beta, [TNF-β]) were also measured. Data was expressed as mean ± standard error of the mean [SEM] values, and the data were analyzed through analysis of variance (ANOVA) followed by the Tukey post hoc test, with significance set at p < 0.05 . The results revealed that sleep deprivation, and the co-administration of alcohol and caffeine impair memory in rats. Sleep deprivation also caused a significant increase in anxiety and anxiety-related behavior, with decreased social interaction, in rats. Locomotive activity was improved in SD rats, especially in those to which alcohol was administered. Sleep deprivation significantly reduced acetylcholinesterase activity among SD rats and those to which alcohol was administered when compared with the controls. The plasma levels of IL-6, IL-10 and TNF-β were significantly increased in SD rats when compared with the controls. The administration of alcohol and caffeine separately, as well as their co-administration, significantly increased cytokine levels in rats.

Assessment of acetylcholinesterase activity in CD9-positive exosomes from patients with Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic dysfunction and associated with abnormalities in the cholinergic system. However, the relationship between PD and cholinergic dysfunction, particularly in exosomes, is not fully understood. We enrolled 37 patients with PD and 44 healthy controls (HC) to investigate acetylcholinesterase (AChE) activity in CD9-positive and L1CAM-positive exosomes. Exosomes were isolated from plasma using antibody-coupled magnetic beads, and their sizes and concentrations were assessed using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Subsequently, the AChE activity in these exosomes was analyzed in relation to various clinical parameters. A significant decrease in AChE activity was observed in CD9-positive exosomes derived from patients with PD, whereas no significant differences were found in L1CAM-positive exosomes. Further analysis with a larger sample size confirmed a substantial reduction in AChE activity in CD9-positive exosomes from the PD plasma, with moderate diagnostic accuracy. The decrease in AChE activity of CD9-positive exosomes did not show an association with cognitive impairment but displayed a trend toward correlation with PD progression. The reduction in AChE activity in CD9-positive exosomes suggests potential peripheral cholinergic dysfunction in PD, independent of the central cholinergic system. The observed alterations in AChE activity provide valuable insights into the association between cholinergic dysfunction and the pathogenesis of PD.

Synthesis and investigation of new indole-containing vinyl sulfide derivatives: In silico and in vitro studies for potential therapeutic applications.

Indoles featuring organosulfur compounds serve as privileged structural scaffolds in various biologically active compounds. This study investigates the biological properties of five synthetic sulphenyl vinyl indoles (3 a-e) using both in silico and in vitro methods. Computational analyses employing Swiss ADME and Molinspiration software reveal the remarkable inhibitory activity of compound 3 d against proteases and kinases (scores of 0.18 and 0.06, respectively). Furthermore, it demonstrates the ability to modulate ionic and G protein-coupled receptors (scores: -0.06 and 0.31, respectively) and serves as a ligand for nuclear receptors (score 0.15). In vitro investigations highlight the compounds' efficacy in countering ABTS+ radical attacks and reducing lipid peroxidation levels. Particularly noteworthy is the superior efficacy of compounds 3 a, 3 b, and 3 e in DPPH (EC50 3 a: 268.5 μM) and TEAC assays (EC50 3 a: 49.9 μM; EC50 3 b: 133.4 μM, and EC50 3 e: 84.9 μM), as well as TBARS levels. Compound 3 c significantly reduces acetylcholinesterase activity, positioning itself as a noteworthy enzyme inhibitor. This study emphasizes the versatile biological potential of synthetic indole derivatives, suggesting their applicability for therapeutic purposes.

Neuroprotective effect of ranolazine improves behavioral discrepancies in a rat model of scopolamine-induced dementia.

Ranolazine (Rn), an antianginal agent, acts in the central nervous system and has been used as a potential treatment agent for pain and epileptic disorders. Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases and the leading factor in dementia in the elderly. We examined the impact of Rn on scopolamine (Sco)-induced dementia in rats. Thirty-two albino male rats were divided into four groups: control, Rn, Sco, and Rn + Sco. A significant decrease in the escape latency in the Morris water maze test after pre-treatment with Rn explained better learning and memory in rats. Additionally, Rn significantly upregulated the activities of the antioxidant enzymes in the treated group compared to the Sco group but substantially reduced acetylcholinesterase activity levels in the hippocampus. Moreover, Rn dramatically reduced interleukin-1 β (IL-1β) and IL-6 and upregulated the gene expression of brain-derived neurotrophic factor (BDNF). Furthermore, in the Sco group, the hippocampal tissue's immunohistochemical reaction of Tau and glial factor activating protein (GFAP) was significantly increased in addition to the upregulation of the Caspase-3 gene expression, which was markedly improved by pre-treatment with Rn. The majority of pyramidal neurons had large vesicular nuclei with prominent nucleoli and appeared to be more or less normal, reflecting the all-beneficial effects of Rn when the hippocampal tissue was examined under a microscope. Our findings indicated that Rn, through its antioxidative, anti-inflammatory, and anti-apoptotic effects, as well as the control of the expression of GFAP, BDNF, and Tau proteins, has a novel neuroprotective impact against scopolamine-induced dementia in rats.

Minocycline mitigated enduring neurological consequences in the mice model of sepsis

AimSepsis-associated encephalopathy is a frequently observed consequence of sepsis, often resulting in chronic brain inflammation and injury, ultimately leading to a range of behavioral abnormalities. This study explores the potential preventive effects of minocycline on the long-lasting outcome of sepsis in a mice model of sepsis. MethodsAdult male C57 mice were subjected to experimental sepsis through a single intraperitoneal injection of 5 mg/kg lipopolysaccharide (LPS). Minocycline administration via oral gavage (12.5, 25, and 50 mg/kg) commenced three days before sepsis induction and continued on the day of induction. Mice underwent behavioral assessments one month post-sepsis, with subsequent brain tissue analysis to investigate oxidative stress markers and cholinergic function. Key findingsOne month following sepsis induction, mice exhibited significant anxiety- and depressive-like behaviors as determined by assessments in the elevated plus maze (EPM), open field, and tail suspension test (TST). Additionally, they displayed impaired recognition memory in the novel object recognition (NOR) test. Brain tissue analysis revealed a notable increase in oxidative stress markers and acetylcholinesterase (AChE) activity in septic mice. Notably, minocycline treatment effectively mitigated the long-term behavioral abnormalities resulting from sepsis, attenuated oxidative stress markers, and reduced AChE activity. SignificanceThese findings underscore the potential of minocycline as a therapeutic intervention during sepsis induction to prevent the enduring behavioral and neurological consequences of experimental sepsis.

Ora-pro-nobis (Pereskia aculeata) supplementation promotes increased longevity associated with improved antioxidant status in Drosophila melanogaster.

This study evaluated the effects of ora-pro-nobis (Pereskia aculeate) flour supplementation on the in vivo basal antioxidant system of Drosophila melanogaster, and its action on the neural modulation observed by the enzyme acetylcholinesterase (AChE). The flies will receive a standard diet with flour incorporated at 5, 10 and 20% for 7 days. There was no change in food consumption, body weight, protein thiol levels and negative geotaxis behavior. The flies showed a reduction in the basal production of reactive species at concentrations of 10 and 20%, while there was a reduction in lipid peroxidation and catalase activity at all concentrations, accompanied by an increase in the levels of non-protein thiols. Superoxide dismutase activity was reduced in the 5 and 20% groups, while the reduction of superoxide anion in the 10% group may have contributed to the increase in longevity also in the 10% group. Longevity increased in groups 5 and 10%. The open field test may be related to the reduction in AChE activity in the 5, 10 and 20% groups. In general, the data show that supplementation with ora-pro-nobis flour at the concentrations tested did not cause toxicity and modulated the cholinergic system, demonstrating a therapeutic potential.

Evaluating the Role of N-Acetyl-L-Tryptophan in the Aβ 1-42-Induced Neuroinflammation and Cognitive Decline in Alzheimer’s Disease

Alzheimer’s disease (AD), a neurodegenerative condition previously known to affect the older population, is also now seen in younger individuals. AD is often associated with cognitive decline and neuroinflammation elevation primarily due to amyloid β (Aβ) accumulation. Multiple pathological complications in AD call for therapies with a wide range of neuroprotection. Our study aims to evaluate the effect of N-acetyl-L-tryptophan (NAT) in ameliorating the cognitive decline and neuroinflammation induced by Aβ 1-42 oligomers and to determine the therapeutic concentration of NAT in the brain. We administered Aβ 1-42 oligomers in rats via intracerebroventricular (i.c.v.) injection to induce AD-like conditions. The NAT-treated animals lowered the cognitive decline in the Morris water maze characterized by shorter escape latency and increased path efficiency and platform entries. Interestingly, the hippocampus and frontal cortex showed downregulation of tumor necrosis factor, interleukin-6, and substance P levels. NAT treatment also reduced acetylcholinesterase activity and total and phosphorylated nuclear factor kappa B and Tau levels. Lastly, we observed upregulation of cAMP response element-binding protein 1 (CREB1) signaling. Surprisingly, our HPLC method was not sensitive enough to detect the therapeutic levels of NAT in the brain, possibly due to NAT concentrations being below the lowest limit of quantification of our validated method. To summarize, the administration of NAT significantly lowered cognitive decline, neuroinflammatory pathways, and Tau protein and triggered the upregulation of CREB1 signaling, suggesting its neuroprotective role in AD-like conditions.

Effects of two alternative plasticizers on the growth hormone-related endocrine system, neurodevelopment, and oxidative stress of zebrafish larvae

In response to the restriction of phthalate plasticizers, acetyl tributyl citrate (ATBC) and acetyl triethyl citrate (ATEC) have been used in medical devices and food packaging. In the present study, the effects of ATBC and ATEC on the development, behavior, growth hormone (GH)-related endocrine system, neurotransmitters, and oxidative stress of zebrafish embryo or larvae were investigated. After exposure of zebrafish to ATBC and ATEC (0, 0.03, 0.3, 3, 30, and 300 μg/L) for 96 h, developmental toxicity, behavioral changes under light/dark condition, changes in hormones and genes involved in GH/insulin-like growth factors (IGFs) axis, changes in hormone, enzyme, and genes related to neurodevelopment, antioxidant enzymes activities were determined. Larvae exposed to 30 or 300 μg/L ATBC showed significant reductions in body length and moving distance and speed, whereas no significant effects on development and locomotor behavior were observed in larvae exposed to ATEC. The contents of GH and IGF-I were significantly reduced in larvae exposed to 3, 30, and 300 μg/L ATBC. Hormonal changes in fish exposed to ATBC are well supported by regulation of genes related to GH (gh1) and the activity of IGF-I (igf1). In fish exposed to ATBC, reduced acetylcholinesterase activity and down-regulation of genes related to the central nervous system development (ache, gap43, mbpa, and syn21) were observed. ATBC increased the production of reactive oxygen species and the levels of superoxide dismutase, catalase, and glutathione peroxidase. Notably, pre-treatment with the classic antioxidant N-acetylcysteine alleviated ATBC-induced GH-related endocrine disruption and neurotoxicity. Our observations showed that exposure to low levels of ATBC could disturb the regulatory systems of GH/IGFs axis and neurobehavior, ultimately leading to developmental inhibition and hypoactivity, and that increased oxidative stress plays a major role in these toxicities.

Effects of Hydrolysates from Silkworms Fed Cudrania tricuspidata Leaves on Improvement of Memory in Rats with Impaired Memory Induced by Scopolamine

This study investigated the memory-improving effects and mechanisms of action of hydrolysate from silkworm fed Cudrania tricuspidata leaves (HSCT) in rats with scopolamine-induced memory impairment. Thirty-two rats were categorized into 4 groups and the experiment was conducted for 6 weeks. The experimental diet groups are as follows: control, control diet; scopolamine, control diet + scopolamine (0.7 mg/kg); HSCT, HSCT diet + scopolamine (0.7 mg/kg); and donepezil, control diet + scopolamine (0.7 mg/kg) + donepezil (1.0 mg/kg). Except for the control group, the experimental groups received scopolamine 0.7 mg/kg intraperitoneally to induce decline in memory. Animal behavioral tests such as the Barnes maze, novel object recognition test, and Y-maze were performed to investigate the effects of HSCT on memory improvement. In addition, brain acetylcholine (ACh) concentration and acetylcholinesterase (AChE) activity were assessed to investigate the mechanism of memory improvement. Results of the animal behavior test suggested that the rats administered HSCT displayed improved memory behavior compared to those administered scopolamine (p &lt; 0.05). The concentration of Ach was increased in the HSCT group compared to the scopolamine group (p &lt; 0.05), and the activity of AChE was significantly reduced (p &lt; 0.05). These results suggest that HSCT effectively improves memory by reducing AChE activity and increasing ACh content in the brains of rats with scopolamine-induced memory impairment. As a natural compound, HSCT has the potential to be used as a material to improve memory.

Long-Term Acetylcholinesterase Depletion Alters the Levels of Key Synaptic Proteins while Maintaining Neuronal Markers in the Aging Zebrafish (Danio rerio) Brain

Introduction: Interventions targeting cholinergic neurotransmission like acetylcholinesterase (AChE) inhibition distinguish potential mechanisms to delay age-related impairments and attenuate deficits related to neurodegenerative diseases. However, the chronic effects of these interventions are not well described. Methods: In the current study, global levels of cholinergic, cellular, synaptic, and inflammation-mediating proteins were assessed within the context of aging and chronic reduction of AChE activity. Long-term depletion of AChE activity was induced by using a mutant zebrafish line, and they were compared with the wildtype group at young and old ages. Results: Results demonstrated that AChE activity was lower in both young and old mutants, and this decrease coincided with a reduction in ACh content. Additionally, an overall age-related reduction in AChE activity and the AChE/ACh ratio was observed, and this decline was more prominent in wildtype groups. The levels of an immature neuronal marker were upregulated in mutants, while a glial marker showed an overall reduction. Mutants had preserved levels of inhibitory and presynaptic elements with aging, whereas glutamate receptor subunit levels declined. Conclusion: Long-term AChE activity depletion induces synaptic and cellular alterations. These data provide further insights into molecular targets and adaptive responses following the long-term reduction of AChE activity that was also targeted pharmacologically to treat neurodegenerative diseases in human subjects.

Perfluorooctanoic acid induces behavioral impairment and oxidative injury in Nauphoeta cinerea nymphs.

Perfluorooctanoic acid (PFOA) is a persistent organic contaminant with potential health threats to both animals and humans. However, the impact of PFOA on insects, which play significant roles in ecosystems, is understudied. We evaluated the toxicological impact of ecologically relevant concentrations of PFOA (0, 25, 50, 100, and 200µg L-1) on Nauphoeta cinerea nymphs following exposure for 42 consecutive days. We analyzed the behavior of the insects with automated video-tracking software and processed the head, midgut, and fat body for biochemical assays. PFOA-exposed insects exhibited significant reductions in locomotory abilities and an increase in freezing time. Furthermore, PFOA exposure reduced acetylcholinesterase activity in the insect head. PFOA exposure increased the activities of superoxide dismutase, glutathione peroxidase, and catalase in the head and midgut, but decreased them in the fat body. PFOA also significantly increased glutathione-S transferase activity, while decreasing glutathione levels in the head, midgut, and fat body. Additionally, PFOA exposure increased reactive oxygen and nitrogen species, nitric oxide, lipid peroxidation, and protein carbonyl contents in the head, midgut, and fat body of the insects. In conclusion, our findings indicate that PFOA exposure poses an ecological risk to Nauphoeta cinerea.

A clinical study and future prospects for bioactive compounds and semi-synthetic molecules in the therapies for Huntington's disease.

A neurodegenerative disorder (ND) refersto Huntington's disease (HD) whichaffects memory loss, weight loss, and movement dysfunctions such as chorea and dystonia. In the striatum and brain, HD most typically impacts medium-spiny neurons. Molecular genetics, excitotoxicity, oxidative stress (OS), mitochondrial, and metabolic dysfunction are a few of the theories advanced to explicit the pathophysiology of neuronal damage and cell death. Numerous in-depth studies of the literature have supported the therapeutic advantages of natural products in HD experimental models and other treatment approaches. This article briefly discusses the neuroprotective impacts of natural compounds against HD models. The ability of the discovered natural compounds to suppress HD was tested using either in vitro or in vivo models. Many bioactive compounds considerably lessened the memory loss and motor coordination brought on by 3-nitropropionic acid (3-NP). Reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and enhanced mitochondrial energy generation have profoundly decreased the biochemical change. It is significant since histology showed that therapy with particular natural compounds lessened damage to the striatum caused by 3-NP. Moreover, natural products displayed varyingdegrees of neuroprotection in preclinical HD studies because of their antioxidantand anti-inflammatory properties, maintenance of mitochondrial function, activation of autophagy,and inhibition of apoptosis. This study highlighted about the importance of bioactive compounds and their semi-synthetic molecules in the treatment and prevention of HD.