Increase In Acetylcholinesterase Activity Research Articles

Blackberry extract prevents lipopolysaccharide-induced depressive-like behavior in female mice: implications for redox status, inflammation, and brain enzymes

ABSTRACT This study evaluated the effects of Rubus sp. extract on behavioral and neurochemical parameters in female mice submitted to experimental model of depression induced by lipopolysaccharide (LPS). The results indicated that Rubus sp. extract protected against depressive-like behavior induced by LPS. Moreover, the administration of Rubus sp. extract was effective in preventing the increase in reactive species and nitrites levels, as well as the decrease in catalase activity induced by LPS in the cerebral cortex. In the serum, the Rubus sp. extract was effective in preventing the decrease in catalase activity induced by LPS. Treatment with Rubus sp. extract attenuated the increase in acetylcholinesterase activity induced by LPS in the cerebral cortex. Finally, blackberry extract also downregulated IL-1β levels in cerebral cortex. In conclusion, our findings demonstrated that treatment with Rubus sp. exerted antidepressant, antioxidant, anticholinesterase and anti-inflammatory effects in a model of depressive – like behavior induced by LPS in female mice. This highlights Rubus sp. as a potential therapeutic agent for individuals with major depressive disorder.

Oxyresveratrol-β-cyclodextrin mitigates streptozotocin-induced Alzheimer's model cognitive impairment, histone deacetylase activity in rats: in silico & in vivo studies

Alzheimer’s disease (AD) is associated with cognitive deficits and epigenetic deacetylation that can be modulated by natural products. The role of natural oxyresveratrol-β-cyclodextrin (ORV) on cognition and histone deacetylase activity in AD is unclear. Herein, in-silico docking and molecular dynamics simulation analysis determined that oxyresveratrol potentially targets histone deacetylase-2 (HDAC2). We therefore evaluated the in vivo ameliorative effect of ORV against cognitive deficit, cerebral and hippocampal expression of HDAC in experimental AD rats. Intracerebroventricular injection of STZ (3 mg/kg) induced experimental AD and the rats were treated with low dose (200 mg/kg), high dose (400 mg/kg) of ORV and donepezil (10 mg/kg) for 21 days. The STZ-induced AD caused cognitive and behavioural deficits demonstrated by considerable increases in acetylcholinesterase activity and escape latency compared to sham control. The levels of malondialdehyde (MDA) and HDAC activity were significantly increased in AD disease group comparison to the sham. Interestingly, the ORV reversed the cognitive-behavioural deficit and prominently reduced the MDA and HDAC levels comparable to the effect of the standard drug, donepezil. The findings suggest anti-AD role of ORV via antioxidant effect and inhibition of HDAC in the hippocampal and frontal cortical area of rats for AD.

Treatment with Blackberry Extract and Metformin in Sporadic Alzheimer's Disease Model: Impact on Memory, Inflammation, Redox Status, Phosphorylated Tau Protein and Insulin Signaling.

Natural products offer promising potential for the development of new therapies for Alzheimer's disease (AD). Blackberry fruits are rich in phytochemical compounds capable of modulating pathways involved in neuroprotection. Additionally, drug repurposing and repositioning could also accelerate the development of news treatments for AD. In light of the reduced brain glucose metabolism in AD, an alternative approach has been the use of the drug metformin. Thus, the aim of this study was to evaluate the effect of treatment with blackberry extract in a model of AD induced by streptozotocin (STZ) and compare it with metformin treatment. Male rats were divided into groups: I-Control; II-STZ; III-STZ + blackberry extract (100mg/kg); IV-STZ + blackberry extract (200mg/kg) and V-STZ + metformin (150mg/kg). The animals received intracerebroventricular injection of STZ or buffer. Seven days after the surgical procedure, the animals were treated orally with blackberry extract or metformin for 21days. Blackberry extract and metformin prevented the memory impairment induced by STZ. In animals of group II, an increase in acetylcholinesterase activity, phosphorylated tau protein, IL-6, oxidative damage, and gene expression of GSK-3β and Nrf2 was observed in the hippocampus. STZ induced a decrease in IL-10 levels and down-regulated the gene expression of Akt1, IRS-1 and FOXO3a. Blackberry extract and metformin prevented the alterations in acetylcholinesterase activity, IL-6, GSK3β, Nrf2, and oxidative damage. In conclusion, blackberry extract exhibits multi-target actions in a model of AD, suggesting new therapeutic potentials for this neurodegenerative disease.

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.

Early exposure to trans fat causes cognitive impairment by modulating the expression of proteins associated with oxidative stress and synaptic plasticity in Drosophila melanogaster

Evidence has shown that consuming trans fatty acids (TFA) during development leads to their incorporation into the nervous tissue, resulting in neurological changes in flies. In this study, Drosophila melanogaster was exposed to different concentrations of hydrogenated vegetable fat (HVF) during development: substitute hydrogenated vegetable fat (SHVF), HVF 10 %, and HVF 20 %. The objective was to evaluate the effects of early trans fat exposure on cognition and associated pathways in flies. The results showed that early TFA exposure provoked a cerebral redox imbalance, as confirmed by increased reactive species (HVF 10 and 20 %) and lipid peroxidation (SHVF, HVF 10, and 20 %), reduced nuclear factor erythroid 2-related factor 2 immunoreactivity (HVF 10 and 20 %), and increased heat shock protein 70 (HVF 20 %), which was possibly responsible for decreasing superoxide dismutase (SHVF, HVF 10, and 20 %) and catalase (HVF 20 %) activities. Furthermore, the presence of TFA in nervous tissue impaired learning (HVF 10 and 20 %) and memory at 6 and 24 h (SHVF, HVF 10, and 20 %). These cognitive impairments may be linked to reduced Shank levels (HVF 20 %) and increased acetylcholinesterase activity (SHVF, HVF 10 and 20 %) observed. Our findings demonstrate that early exposure to trans fat leads to cerebral redox imbalance, altering proteins associated with stress, synaptic plasticity, and the cholinergic system, consequently leading to cognitive impairment in flies.

Assessment of Acetylcholinesterase Enzyme (AChE) Activity in the Developing Brain of TSD Lizard, Calotes Versicolor (Daud.)

Acetylcholinesterase (AChE) is a critical enzyme in the neuronal cholinergic system of vertebrates. It is one of the efficient cholinesterases that is involved in the termination of acetylcholine-mediated neurotransmission, rapidly hydrolyzing acetylcholine into acetate and choline. Barring a few reports on the distribution/presence of AChE enzyme activity in the adult reptilian species there are nil reports on the presence of this enzyme activity in the developing brain. Hence, the present investigation aims to evaluate AChE enzyme activity in the developing brain of an oviparous lizard, Calotes versicolor which exhibits a novel Female-Male-Female-Male (FMFM) pattern of temperature-dependent sex determination (TSD). The eggs were collected during breeding season, padded with moist cotton, and incubated in an incubator at 30o C. The whole brain from the embryos was collected during different developmental stages from oviposition (Stage 27) to hatching (stage 42). The AChE enzyme activity was quantified in the brain, according to Ellman’s protocol using a spectrophotometer. The findings reveal that the onset of AChE enzyme activity is observed as early as at oviposition, which reflects the early action of AChE activity in the developing brain. The observed results albeit indirectly suggest the involvement of AChE enzyme activity in the morphogenetic process. Further, an exponential increase in AChE activity during the post-gonadal differentiation phase indicates age-related elevation in AChE enzyme activity which in turn unveils its involvement in neuronal transmission of the embryonic brain. Besides, this specific AChE enzyme activity in the developing brain of Calotes versicolor represents a conserved pattern for the cholinergic system in vertebrates.

Direct Head Injection of Streptozotocin elicits Behavioral Deficiencies and Neurochemical Alterations Characteristic of Neurodegeneration in Lobster Cockroach; Nauphoeta cinerea (Blattodea: Blaberidae) Model

AbstractBackgroundNeurodegeneration diseases are a group of diseases like Alzheimer’s disease that are characterized by poor cognitive abilities, neuromuscular deficiencies and locomotion difficulties. The goal of biomedical research is to seek to explore suitable experimental models to study such neurological disorders. Such suitable models must underscore the 3Rs of alternative research models ‐ replacement, reduction and refinement. The lobster cockroach (Nauphoeta cinerea) is one such model that is gaining global attention for their suitability to study human‐related diseases. Therefore, this study aims to model neuromuscular deficiencies and neurodegeneration associated with impaired glucose homeostasis in lobster cockroach (Nauphoeta cinerea).MethodAcute neurotoxicity was achieved by injecting 74 and 740 nm streptozotocin (STZ) injection per cockroach head and the cockroaches were monitored for 7 days. Thereafter, their survival rate, mortality and behavioral profiles for neuromuscular function including the total time immobile, total distance traveled, time spent in periphery and average speed were assessed on the seventh day, after which the cockroaches were assayed for biomarkers of neurodegeneration and oxidative stress.ResultThe results showed that the survival rate, average speed and total distance traveled were reduced significantly, while STZ increased the mortality, time spent in periphery and total time immobile. Furthermore, STZ induced an increase in acetylcholinesterase activity, lipid peroxidation and total reactive oxygen species. In addition, the results also suggest an impairment in glucose‐trehalose conversation mechanism.ConclusionThese results are obvious indications of behavioral impairments and metabolic disruptions which affect neuromuscular function and are indices of neurodegeneration. This therefore, suggests that direct injection of STZ to cockroach head is a useful, effective and reproducible model in evaluating neuromuscular deficiencies and neurodegeneration associated with brain glucose metabolic dysregulation.

Psychopharmacological Investigation to Explore the Neuroprotective Mechanism of Quercetin and Naringenin in an Experimental Model of Insulin Resistance and Related Cognitive Dysfunction

AbstractBackground Alzheimer’s disease is a brain ailment that causes cell degradation and is the leading cause of dementia, which is defined by a deterioration in thinking and independence in routine everyday activities. Insulin possesses neuroprotective and memory‐enhancing effects indicating a permissive function for insulin in cognition. Defective insulin signaling promotes Aβ aggregation and accelerates Aβ formation in the brain. Based on this evidence, Alzheimer’s is also defined as diabetes of the brain or Type 3 Diabetes.MethodDiabetes was induced in mice by Alloxan (100mg/kg) and sucrose 35% solution. Glucose level was monitored, and test drugs were given accordingly. Behavioral models employed in the current study were elevated plus maze, morris water maze, actophotometer, and novel object recognition test. Biochemicals performed were all mitochondrial complexes, glutathione level, protein carbonyl level, lipid peroxidase, and acetylcholinesterase activity. Histopathological evaluation of the hippocampal region was carried out under a bright field microscope.ResultAlloxan administration produced significant hyperglycemia characterized by a significant increase in serum glucose level as compared to the naïve. During the acquisition test (learning), alloxan‐treated mice significantly delayed the escape latency period to reach the submerged platform as compared to the naïve group. However, quercetin and naringenin administration significantly improved memory performance. In novel object recognition, alloxan treated spent more time near the familiar object, and the treatment group spent more time near the novel object. Alloxan treatment also disrupted the mitochondrial levels and lowered the antioxidant enzyme levels, whereas the treatment group significantly reversed the changes.ConclusionIn the present study, alloxan administration caused significant impairment in cognitive behavior as evidenced by the Morris water maze (MWM) test, increased fasting blood glucose oxidative stress [through alteration of endogenous antioxidant markers i.e. superoxide dismutase (SOD), and catalase antioxidant enzyme activity and reduced glutathione (GSH) levels and oxidative stress markers i.e. reactive oxygen species (ROS) and protein carbonyls levels] and increased acetylcholinesterase activity in different areas of the brain (frontal cortex and hippocampus). Administration of quercetin and naringenin in different doses significantly reversed alloxan administration‐induced behavioral, biochemical, and cellular alteration in both the frontal cortex as well as in hippocampus.

Alkaloid-rich extract of Buchholzia coriacea seed mitigate the effect of copper-induced toxicity in Drosophila melanogaster

AbstractBuchholzia coriacea is known for its anti-oxidative, anti-inflammatory, and anti-diabetic properties. This study evaluated the effect of alkaloid-rich extract of Buchholzia coriacea seed (ArEBCs) against copper-induced toxicity in Drosophila melanogaster. The flies were exposed to graded doses (25 to 200 mg/kg diet) of ArEBCs for 12 days and thereafter, a survival test was carried out to determine the safe and therapeutic doses used in the ameliorative study. For this, flies were exposed to CuSO4 (1 mM) alone or in combination with ArEBCs (25 and 50 mg/kg diet) for 5 days. Locomotor activity and biochemical assays such as glucose (GLU) level, acetylcholinesterase (AChE) activity, malonaldehyde (MDA) and antioxidant biomarkers (catalase and reduced glutathione) were performed to assess the effect of ArEBCs on the copper-induced flies. Copper-exposed flies showed reduced survival rates and disrupted locomotor activity when compared to the control flies. In addition, a significant (p &lt; 0.05) increase in AChE activity, GLU and MDA levels and a decrease in the antioxidant biomarkers activities were observed in the copper-exposed flies. Treatment of flies with ArEBCs mitigated the negative effect of copper on the flies by increasing the survival rate of the flies, reducing the activities of AChE, GLU and MDA. The activities of the cellular antioxidant status were also significantly (p &lt; 0.05) increased. This study suggests that ArEBCs could mitigate the effect of copper-induced oxidative damage in Drosophila melanogaster and could be considered a potential therapeutic agent against copper-induced oxidative damage.

Omega-3 fatty acids prevent nicotine withdrawal-induced impairment of learning and memory via affecting oxidative status, inflammatory response, cholinergic activity, BDNF and amyloid-B in rat hippocampal tissues

In the present study, the main objective was to reveal whether treatment by Omega-3 fatty acids could prevent the adverse effects of adolescent nicotine withdrawal on spatial and avoidance memory in male rats. For this purpose, Morris water maze and passive avoidance tests were performed on male Wistar rats and the hippocampal levels of oxidative stress markers, inflammatory indices, brain-derived neurotrophic factor, nitrite, amyloid-B and acetylcholinesterase (AChE) were measured. Moreover, density of dark neurons were assessed in CA1 and CA3 regions. Results showed that adolescent nicotine exposure followed by a period of drug cessation exacerbates the behavioral indices of learning and memory through affecting a variety of biochemical markers within the hippocampal tissues. These changes lead to elevation of oxidative and inflammatory markers, reduction of neurotrophic capacity and increased AChE activity in hippocampal tissues. In addition, it was observed that co-administration of nicotine with Omega-3 fatty acids significantly prevents nicotine withdrawal-induced adverse effects through restoration of the mentioned biochemical disturbances. Therefore, we suggest administration of Omega-3 fatty acids as a safe, inexpensive and effective therapeutic strategy for prevention of memory dysfunctions associated with nicotine abstinence during adolescence.

Neuroprotective and anti-amnesic effects of Laurus Nobilis essential oil against scopolamine-induced memory deficits in mice brain

Ethnopharmacological relevanceLaurus nobilis L. (Lauraceae family) has been widely used in traditional Tunisian medicine for the treatment of different health problems such as rheumatism and some neurological disorders. AimIn this study, the essential oil obtained from Laurus nobilis L. species from Tunisia (LEO) was studied for its chemical composition and anti-amnesic activities on memory impairment caused by scopolamine injection in mice. The major compounds of LEO oil, 1,8-cineole and, α-terpinyl acetate were docked with AChE (Acetylcholinesterase), using Autodock Vina and Discovery Studio visualizer software. Materials and methodsThe Morris water maze (MWM) tests and the Y maze were used to assess the anti-amnesic effects of LEO in mice with scopolamine-induced memory impairments. In brain tissues, the levels of biomarkers, enzyme activity, and protein expression related to the cholinergic system were measured. ResultsChronic administration of scopolamine led to a significant decline in cognitive performance in both the Morris Water Maze (MWM) and Y maze tests, accompanied by pronounced oxidative damage and a significant increase in acetylcholinesterase activity compared to the other groups. However, compared to the scopolamine group, treatment with LEO (100 mg/kg) significantly enhanced cognitive function and ameliorated the oxidative damage (p < 0.05 versus scopolamine) ConclusionThis study demonstrates the beneficial effect of LEO on scopolamine-induced dementia in mice, potentially achieved through the modulation of cholinergic activity and antioxidant properties. The docking analysis of the major compounds, 1,8-cineole and α-terpinyl acetate, further substantiates their potential as memory enhancers.

Anticholinesterase activity and antioxidant effect of vitamin E in aluminium chloride induced toxicity in &lt;i&gt;Drosophila melanogaster&lt;/i&gt;

Background: Aluminium chloride (AlCl3) toxicity has been reported to be linked with impaired locomotion, memory, learning, oxidative stress and impairment of cholinergic function which are synonymous with features seen in Alzehmiers disease (AD). Vitamin E has been put forward as a possible therapeutic intervention for AD. However, there are controversies as to whether Vitamin E is beneficial in the management of AD. Anticholinesterase activity and antioxidant potential of vitamin E was evaluated in aluminium chloride induced toxicity in Drosophila Melanogaster.Methods: A 2.5mg dose of Vitamin E was considered the appropriate standard for this study after exposure of flies to varying doses of vitamin E in a 15-day survival study. Group I served as control while group II were treated with 40mM aluminium chloride (AlCl3) via their diet. Group III were treated with 2.5mg of Vitamin E via their diet and Group IV were co-administered with 40 mM AlCl3 and 2.5mg of Vitamin E via their diet. The flies were maintained on these treatments at room temperature for seven (7) days. Negative geotaxis was carried out to assess for locomotor performance (climbing activity). The impact of 40 mM AlCl3 and/0r 2.5mg of Vitamin E on the survival rate of flies was also evaluated by carrying out a 15-day survival study At the end of the experimental period, the flies were homogenized and the supernatants were used to assay for, malonaldehyde (MDA) concentration, acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities.Results: AlCl3 significantly reduced (P&lt;0.05) the survival rate, decreased the climbing activity of flies, elevated MDA concentration and AChE activities of flies. SOD, CAT and GST activities were also significantly reduced (P&lt;0.05) in AlCl3 treated flies. In the co treatment protocol, vitamin E was able to significantly improve (P&lt;0.05) the survival rate, improved their climbing activity and ameliorated AlCl3 increase in AChE activity and MDA concentration in these flies. In addition, vitamin E significantly attenuated (P&lt;0.05) AlCl3 induced decrease in SOD, CAT and GST activities.Conclusion: This study has shown that vitamin E has both antioxidant and anti-cholinesterase activities and could be of therapeutic benefits against AlCl3 induced toxicity and associated diseases like Alzheimer’s disease.

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents.

Alzheimer's disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults. Pathogenic factors, such as oxidative stress, an increase in acetylcholinesterase activity, mitochondrial dysfunction, genotoxicity, and neuroinflammation are present in this syndrome, which leads to neurodegeneration. Neurodegenerative pathologies such as Alzheimer's disease are considered late-onset diseases caused by the complex combination of genetic, epigenetic, and environmental factors. There are two main types of Alzheimer's disease, known as familial Alzheimer's disease (onset < 65 years) and late-onset or sporadic Alzheimer's disease (onset ≥ 65 years). Patients with familial Alzheimer's disease inherit the disease due to rare mutations on the amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) genes in an autosomal-dominantly fashion with closely 100% penetrance. In contrast, a different picture seems to emerge for sporadic Alzheimer's disease, which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology. Importantly, the fundamental pathophysiological mechanisms driving Alzheimer's disease are interfaced with epigenetic dysregulation. However, the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer's disease or following injury or stroke in humans. In recent years, there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer's disease. Through epigenetic mechanisms, such as DNA methylation, non-coding RNAs, histone modification, and chromatin conformation regulation, natural compounds appear to exert neuroprotective effects. While we do not purport to cover every in this work, we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer's disease-related genes.

Beta-caryophyllene mitigates the cognitive impairment caused by repeated exposure to aspartame in rats: Putative role of BDNF-TrKB signaling pathway and acetylcholinesterase activity

Aspartame (ASP) is a common sweetener, but studies show it can harm the nervous system, causing learning and memory deficits. β-caryophyllene (BCP), a natural compound found in foods, including bread, coffee, alcoholic beverages, and spices, has already described as a neuroprotector agent. Remarkably, ASP and BCP are commonly consumed, including in the same meal. Therefore, considering that (a) the BCP displays plenty of beneficial effects; (b) the ASP toxicity; and (c) that they can be consumed in the same meal, this study sought to investigate if the BCP would mitigate the memory impairment induced by ASP in rats and investigate the involvement of the brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrKB) signaling pathway and acetylcholinesterase (AChE) activity. Young male Wistar rats received ASP (75 mg/kg; i.g.) and/or BCP (100 mg/kg; i.p.) once daily, for 14 days. At the end of the treatment, the animals were evaluated in the open field and object recognition tests. The cerebral cortex and hippocampus samples were collected for biochemical and molecular analyses. Results showed that the BCP effectively protected against the cognitive damage caused by ASP in short and long-term memories. In addition, BCP mitigated the increase in AChE activity caused by ASP. Molecular insights revealed augmented BDNF and TrKB levels in the hippocampus of rats treated with BCP, indicating greater activation of this pathway. In conclusion, BCP protected against ASP-induced memory impairment. AChE activity and the BDNF/TrkB signaling pathway seem to be potential targets of BCP modulatory role in this study.

Ferulago angulata Methanolic Extract Protects PC12 Cells Against Beta-amyloid-induced Toxicity.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease. Beta-amyloid (Aβ)-induced neurotoxicity has a pivotal role in AD pathogenesis; therefore, the modulation of Aβ toxicity is the promising therapeutic approach to control the disease progression. Medicinal plants because of their multiple active ingredients are effective in complex diseases, such as AD. Therefore, several studies have studied medicinal plants to find an effective treatment for AD. Ferulago angulata is a medicinal plant with antioxidant and neuroprotective activity. The present study was done to assess the protective effect of the methanolic extract of Ferulago angulate on Aβ-induced toxicity and oxidative stress in PC12 cells. The methanolic extract of aerial parts of the plant was prepared by the maceration method. PC12 cells were cultured according to a standard protocol. PC12 cells were incubated for 24 hours with Aβ alone, and Aβ in combination with various concentrations of the F. angulata extract. Cell viability was determined by the methyl thiazole tetrazolium (MTT) assay. Also, reactive oxygen species (ROS) production and the activity of acetylcholine esterase (AChE), glutathione peroxidase (GPx), and caspase-3 enzymes were measured. The extract dose-dependently protected PC12 cells against Aβ-induced cell death. Also, Aβ increased ROS production, AChE, and caspase-3 activity, and decreased the GPx activity, which all were ameliorated by F. angulata extract. F. angulata extract protects against Aβ-induced oxidative stress and apoptosis. These effects may be due to the antioxidant and anticholinesterase activity of the extract. It is recommended to assess F. angulata extract as an anti-AD agent. Ferulago angulata extract dose-dependently ameliorates Aβ-induced cytotoxicity in PC12 cells.Aβ induced oxidative stress in PC12 cells, which was attenuated by the F. angulata extract.Aβ increased acetylcholinesterase activity in PC12 cells, which was prevented by the F. angulata extract. Alzheimer's disease (AD) is a common form of dementia in the elderly with a complex pathophysiology. Beta-amyloid (Aβ)- induced neurotoxicity plays a pivotal role in AD progression. So far, there is no cure for AD. Medicinal plants contain various pharmacologically active compounds that make them suitable for the treatment of complex diseases. In this study, the anti-AD effect of F. angulata extract was investigated by assessing its protective effect against Aβ-induced toxicity in PC12 cells F. angulata extract improved Aβ-induced toxicity by diminishing oxidative stress and apoptosis. Therefore, F. angulata extract merits further studies for use in the treatment of AD.

Cajanus cajan (L) Millsp. seed extract ameliorates scopolamine-induced amnesia through increase in antioxidant defense mechanisms and cholinergic neurotransmission.

Decline in cholinergic function and oxidative/nitrosative stress play a central role in Alzheimer's disease (AD). Previous quantitative HPLC profiling analysis has revealed the presence of Pinostrobin, formononetin, vitexin and other neuroprotective flavonoids in Cajanus cajan seed extract. This study was designed to investigate the protective action of Cajanus cajan ethanol seed extract (CC) on learning and memory functions using scopolamine mouse model of amnesia. Materials and methods: Adult mice were pretreated with CC (50, 100, or 200mg/kg, p.o) or vehicle (10ml/kg, p.o) for 16 days consecutively. Scopolamine, a competitive muscarinic cholinergic receptor antagonist (1mg/kg, i.p.) was given an hour after CC pretreatment from days 3 to 16. The mice were subjected to behavioural tests from day 11 (open field test (OFT)/ Y-maze test (YMT) and Morris water maze task (MWM) from days 12-16. Animals were euthanized 1h after behavioral test on day 16 and discrete brain regions isolated for markers of oxidative stress and cholinergic signaling. Molecular docking analysis was undertaken to predict the possible mechanism(s) of CC-induced anti-amnesic action. pre-administration of CC significantly reversed working memory and learning deficits caused by scopolamine in YMT and MWM tests, respectively. Moreover, CC prevented scopolamine-induced oxidative and nitrosative stress radicals in the hippocampus evidenced in significant increase in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities with a marked decrease in malondialdehyde (MDA) production, as well as significant inhibition of hippocampal scopolamine-induced increase in acetylcholinesterase activity by CC. The molecular docking analysis showed that out of the 19 compounds, the following had the highest binding affinity; Pinostrobin (-8.7 Kcal/mol), friedeline (-7.5kCal/mol), and lupeol (-8.2 Kcal/mol), respectively, to neuronal muscarinic M1 acetylcholine receptor, α7 nicotinic acetylcholine receptor and amyloid beta peptide binding pockets, which further supports the ability of CC to enhance neuronal cholinergic signaling and possible inhibition of amyloid beta aggregation. This study showed that Cajanus cajan seeds extract improved working memory and learning through enhancement of cholinergic signaling, antioxidant capacity and reduction in amyloidogenesis.

Molecular Insights on the Modulated Acetylcholinesterase Inhibition Activity of Tacrine Adsorbed on Biocompatible Graphene Oxide

AbstractGraphene oxide (GO) based nano‐formulation has gained much attention because of its carbonaceous composition with biologically benign properties. In this study, the interactions of GO with tacrine (TAC), an FDA approved Alzheimer's disease (AD) drug, are explored using various analytical tools and theoretical modeling techniques. Furthermore, the modulatory effect of these nano‐conjugates toward the in‐vitro catalytic activity of the neurodegenerative enzyme acetylcholinesterase (AChE) is also quantified. The maximal rate for enzyme inhibition in presence of the nanoconjugate decreases up to an extent of 16 and 34 % in comparison with TAC and GO, respectively. Interestingly, these results are in sharp contrast to the increased AChE activity on adsorption into spherical gold and silver nanoparticles. The current findings demonstrate the synergistic use of TAC−GO hybrid material with augmented AChE inhibition efficacy towards the treatment of Alzheimer's disease (AD). Additionally, GO presents a sustainable alternative for biomedical applications to inorganic equivalents.

P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice.

Introduction: Sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice. Methods: Sepsis was induced in wild-type (WT), P2X7-/-, and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated. Results: Initially, we observed that both WT and P2X7-/- sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba-1) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7-/- sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10). Conclusion: The modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsis-associated encephalopathy, being considered an important therapeutic target.

Realistic concentrations of Bisphenol-A trigger a neurotoxic response in the brain of zebrafish: Oxidative stress, behavioral impairment, acetylcholinesterase inhibition, and gene expression disruption

Bisphenol A (BPA) is a micro-pollutant found in various environmental matrices at concentrations as low as ng/L. Recent studies have shown that this compound can cause oxidative damage and neurotoxic effects in aquatic organisms. However, there is a lack of research investigating the effects of BPA at environmentally relevant concentrations. Therefore, this study aimed to assess the neurotoxic effects of acute BPA exposure (96 h) at environmentally relevant concentrations (220, 1180, and 1500 ng/L) in adult zebrafish (Danio rerio). The Novel Tank trial was used to evaluate fish swimming behavior, and our results indicate that exposure to 1500 ng/L of BPA reduced the total distance traveled and increased freezing time. Furthermore, the evaluation of biomarkers in the zebrafish brain revealed that BPA exposure led to the production of reactive oxygen species and increased acetylcholinesterase activity. Gene expression analysis also indicated the overexpression of mbp, α1-tubulin, and manf in the zebrafish brain. Based on our findings, we concluded that environmentally relevant concentrations of BPA can cause anxiety-like behavior and neurotoxic effects in adult zebrafish.

The simultaneous action of acute paradoxical sleep deprivation and hypothyroidism modulates synaptosomal ATPases and acetylcholinesterase activities in rat brain

BackgroundThyroid dysfunctions as well as sleep abnormalities are usually followed by neurological, psychiatric and/or behavioral disorders. On the other hand, changes in the brain adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) activities show significant importance in pathogenetic pathways in the evolution of numerous neuropsychiatric diseases. MethodsThis study aimed to evaluate the in vivo simultaneous effects of hypothyroidism and paradoxical sleep deprivation for 72 h on synaptosomalATPases and AChE activities of whole rat brains.In order to induce hypothyroidism, 6-n-propyl-2-thiouracil was administrated in drinking water during 21 days. The modified multiple platform method was used to induce paradoxical sleep deprivation. The AChE and ATPases activities were measured using spectrophotometric methods. ResultsHypothyroidism significantly increased the activity of Na+/K+-ATPase compared to other groups, while at the same time significantly decreased AChE activity compared to the CT and SD groups. Paradoxical sleep deprivation significantly increased AChE activity compared to other groups. The simultaneous effect of hypothyroidism and sleep deprivation reduced the activity of all three enzymes (for Na+/K+-ATPase between HT/SD and HT group p < 0.0001, SD group p < 0.001,CT group p = 0.013; for ecto-ATPases between HT/SD and HT group p = 0.0034, SD group p = 0.0001, CT group p = 0.0007; for AChE between HT/SD and HT groupp < 0.05, SD group p < 0.0001, CT group p < 0.0001). ConclusionsThe effect of simultaneous existence of hypothyroidism and paradoxical sleep deprivation reduces the activity of the Na+/K+-ATPase, ecto-ATPases, and AChE, what is different from individual effect of hypothyroidism and paradoxical sleep deprivation itself. This knowledge could help in the choice of appropriate therapy in such condition.