Reduced Acetylcholinesterase Activity Research Articles

Amelioration of oxidative stress and neuroinflammation in lipopolysaccharide-induced memory impairment using Rosmarinic acid in mice.

Oxidative stress plays a pivotal part in the manifestation of neuroinflammation, which further leads to neurodegenerative diseases like Alzheimer's disease (AD). Systemic administration of lipopolysaccharide (LPS) induces neuroinflammation resulting in memory impairment (MI) and cognitive decline. In this study, we evaluated whether prophylactic administration of Rosmarinic acid (RA), a naturally occurring compound, exerts a neuroprotective effect in LPS-induced MI and cognitive decline. Herein, Swiss albino mice were pre-treated with RA (0.5mg/kg and 1mg/kg i.p.) for 28 days and were intermittently exposed to LPS (0.25mg/kgi.p.) for 7 days. LPS caused poor memory retention and increased cognitive decline in Morris water maze (MWM) and Y maze paradigms respectively. Additionally, LPS increased oxidative stress which was denoted by a decrease in superoxide dismutase (SOD) activity, decrease in reduced glutathione (GSH) levels, and increased lipid peroxidation in the brain. Imbalance in the cholinergic system was analyzed by measuring the acetylcholinesterase (AChE) activity. Pre-treatment with RA improved memory and behavioral disturbances by alleviating oxidative stress and AChE activity. LPS augmented levels of tumor necrosis factor (TNF-α), interleukin (IL)-6, caspase-3, and c-Jun. Pre-treatment with RA revitalized the elevated levels of proinflammatory cytokines and apoptotic proteins. In conclusion, this study showcases the amelioration of MI by RA in LPS-challenged memory and cognitive decline, which could be credited to its anti-oxidant effect, inhibitory effect on both proinflammatory cytokines and apoptotic regulators, and reduction in AChE activity.

Toxicity of polystyrene nanoplastics in dragonfly larvae: An insight on how these pollutants can affect bentonic macroinvertebrates

Although nanoplastics (NPs) are known to be toxic to several groups of animals, the effects of such a toxicity on freshwater benthic macroinvertebrate communities remain unknown. Thus, the aim of the current study is to test the hypothesis that polystyrene nanoplastics (PS NPs) (34 μg/L - 48 h of exposure) lead to biochemical damage in Aphylla williamsoni larvae. Data have evidenced high bioaccumulation factor in the analyzed individuals; this finding indicates that, similar to sediments, water is also part of aquatic systems and favors PS NPs retention in dragonfly larvae. Despite the lack of evidence about the interference of these pollutants in the nutritional status of the analyzed animals, their bioaccumulation was associated with REDOX imbalance featured by concomitant increase in the number of evaluated oxidative stress biomarkers (nitric oxide and lipid peroxidation) and antioxidants (antioxidant activity against the DPPH radical and the superoxide dismutase enzyme). On the other hand, the reduced acetylcholinesterase activity observed in larvae exposed to PS NPs has suggested the neurotoxic effect of these pollutants, with potential impact on their nerve and neuromuscular functions. Therefore, the current study is pioneer in showing that PS NPs can affect the health of the investigated larvae, even at small concentrations, for short exposure-time; this outcome reinforces the ecotoxicological risk of these pollutants for freshwater benthic macroinvertebrates.

Uncaria tomentosa improves cognition, memory and learning in middle-aged rats.

Aging accelerates neurodegeneration, while natural and safe neuroprotective agents, such as Uncaria tomentosa, may help to overcome this problem. This study assessed the effects of U. tomentosa extract treatment on the aging process in the brain of Wistar rats. The spatial memory and learning, acetylcholinesterase (AChE) activity, and DNA damage were assessed. Animals of 14months were tested with different doses of U. tomentosa (5mg/kg, 15mg/kg, and 30mg/kg) and with different durations of treatment (one month and one year). In the Morris Water Maze (MWM), the escape latency was significantly (p<0.0001) shorter in rats that received 5mg/kg, 15mg/kg, and 30mg/kg of U. tomentosa for both one month and one year of treatment. There was a significant difference in time spent at the platform zone (p<0.05) of the middle-aged rats treated with U. tomentosa extract for one year when compared to the control rats. The cortex and hippocampus of rats treated with U. tomentosa for one year showed significant (p>0.05) reduction in AChE activity. DNA damage index on cortex was significantly lower (p<0.05) in animals treated with 30mg/kg of U. tomentosa for one month while all the tested doses demonstrated significant (p<0.001) reductions in DNA damage index in animals treated for one year. In conclusion, U. tomentosa may represent a source of phytochemicals that could enhance memory activity, repair DNA damage, and alter AChE activity, thereby providing neuroprotection during the aging process.

Evaluation of Mn exposure in the male reproductive system and its relationship with reproductive dysfunction in mice

Manganese (Mn) is essential for animal development and homeostasis. However, anthropogenic activities increase the concentration of Mn in the environment and lead to increased risk of exposure to high doses of the metal. Thus, this study aimed to evaluate the effect of high doses of Mn on the male reproductive system of swiss mice. The 22-day old mice were randomly sorted into four groups and exposed to 0 (control), 15, 30 and 60 mg of MnCl2/kg/day, via daily gavages for 45 days. After the exposure, the mice were euthanized and sperm, hormonal and oxidative stress endpoints were evaluated in the testis, seminal vesicle and hypothalamus. Exposure to Mn promoted weight reduction of androgen-dependent organs, as well as alteration of the levels of fecal androgenic metabolites. Sperm parameters were drastically affected in all treated groups and the antioxidants tested (catalase and glutathione-disulfide reductase activities, and non-protein thiols content) decreased in the testis. However, only a few endpoints were altered in the seminal vesicle. For the hypothalamus, there was a reduction in acetylcholinesterase activity, suggesting a neurotoxic potential of Mn. In conclusion, Mn may affect the hypothalamic-gonadal axis by impairing the development of androgen-dependent organs, testicular redox status and Leydig cell maturation.

Biochemical and ultrastructural changes in the ovaries of red palm weevil, Rhynchophorus ferrugineus (Coleoptera: Curculionidae) following acute imidacloprid poisoning

Abstract This study aims to inspect the effects of Imidacloprid (IMI) acute toxicity in the ovaries of the red palm weevil (Rhynchophorus ferrugineus). The LC50 of IMI was determined to be 15.7 ppm. We assessed the biochemical changes resulting from treatment with four IMI concentrations (10, 15, 20 and 30 ppm). IMI reduced acetylcholine esterase activity in a dose-dependent manner. Glutathione (GSH) content decreased with increasing concentration of IMI; however, GSH was not affected and accompanied by an increase in catalase activity with the highest concentration of IMI. Lipid peroxidation increased steadily as IMI concentration increased. Based on the ultrastructural analyses of the follicle cells and the ooplasm of developing oocytes, acute IMI toxicity produced damaged yolk bodies, pale nuclei, and shrinking microvilli. Fractionation of rough endoplasmic reticulum, deformed mitochondria, and autophagic bodies were also observed. In conclusion, these ovarian pathobiochemical changes could be used as biomarkers of acute IMI exposure.

Does the perigestational exposure to chlorpyrifos and/or high-fat diet affect respiratory parameters and diaphragmatic muscle contractility in young rats?

The perinatal period is characterized by developmental stages with high sensitivity to environmental factors. Among the risk factors, maternal High-Fat Diet (HFD) consumption and early-life pesticide exposure can induce metabolic disorders at adulthood. We established the effects of perigestational exposure to Chlorpyrifos (CPF) and/or HFD on respiratory parameters, sleep apnea and diaphragm contractility in adult rats. Four groups of female rats were exposed starting from 4 months before gestation till the end of lactation period to CPF (1 mg/kg/day vs. vehicle) with or without HFD. Sleep apnea and respiratory parameters were measured by whole-body plethysmography in male offspring at postnatal day 60. Then diaphragm strips were dissected for the measurement of contractility, acetylcholinesterase (AChE) activity, and gene expression. The perigestational exposure to CPF and/or HFD increased the sleep apnea index but decreased the respiratory frequency. The twitch tension and the fatigability index were also increased, associated with reduced AChE activity and elevated mRNA expression of AChE, ryanodine receptor, and myosin heavy chain isoforms. Therefore, the perigestational exposure to either CPF and/or HFD could program the risks for altered ventilatory parameters and diaphragm contractility in young adult offspring despite the lack of direct contact to CPF and/or HFD.

Bisphenol A exposure is involved in the development of Parkinson like disease in Drosophila melanogaster

The pathogenesis of Parkinson's disease has not been fully clarified yet but its cause is known to be multifactorial. One of these factors is oxidative stress induced by exposure to environmental toxifiers. We studied the effect of Bisphenol A (BPA) at concentrations of 0.5 mM and 1 mM, the concentration of 1 mM corresponding to Lowest Observed Adverse Effect Level (LOAEL) for humans in adult Drosophila melanogaster. The BPA induced oxidative stress was established by increased levels of malondialdehyde, reactive species, and decreased activity of the antioxidant enzymes superoxide dismutase and catalase, and detoxificant enzyme glutathione-S-transferase. Associated with oxidative stress, there was a reduction of acetylcholinesterase activity and a reduction of dopamine levels, which are related to the decreased locomotion activity as observed in negative geotaxis, open field and equilibrium behaviors in group exposed to 1 mM of BPA. Oxidative stress also impaired mitochondrial and cellular metabolic activity in the head causing an increase in the mortality of flies exposed to both BPA concentrations. Therefore, BPA induced Parkinsonian-like changes in flies and it is possible that the oxidative stress is closely related to this effect, providing new insights for future studies.

Dietary zinc supplement militates against ketamine-induced behaviours by age-dependent modulation of oxidative stress and acetylcholinesterase activity in mice.

The potential differential modulatory effects of zinc-supplemented diet on ketamine-induced changes in behaviours, brain oxidative stress, acetylcholinesterase activity, and zinc (ZN) levels were examined in prepubertal and aged mice. Aged and prepubertal mice were divided into 2 groups consisting of 80 aged and 80 prepubertal mice, each having 8 treatment groups of 10 animals each. The treatment groups are: vehicle control group (fed standard diet and given intraperitoneal {ip} normal saline), three groups fed ZN-supplemented diet (at 25, 50 and 100mg/kg of feed) and given ip normal saline, ketamine control group (fed standard diet and given ip ketamine), and finally another three groups fed ZN-supplemented diet (at 25, 50 and 100mg/kg of feed) and given ip ketamine. Intraperitoneal normal saline (at 2ml/kg/day) or ketamine (at 30mg/kg/day) were administered during the last 10days of study. On day 60, animals were exposed to the open-field, Y-maze, radial-arm maze, and elevated plus maze following which they were euthanised; blood and brain homogenate were used for assessment of biochemical parameters. Zinc supplementation was associated with an increase in food intake and body weight (in both age groups), a reduction in ketamine-induced increase in locomotion, rearing and grooming, and significantly higher working-memory scores (compared to ketamine control). Also, there was a decrease in anxiety-related behaviours, enhanced antioxidant status, reduced lipid peroxidation, and reduced acetylcholinesterase activity. In conclusion, dietary ZN supplementation was associated with variable degrees of prevention of ketamine-induced changes, depending on the age of animals.

D-Ribose-L-cysteine attenuates lipopolysaccharide-induced memory deficits through inhibition of oxidative stress, release of proinflammatory cytokines, and nuclear factor-kappa B expression in mice.

D-Ribose-L-cysteine (DRLC), an analog of cysteine that boosts glutathione (GSH) content, has been reported to mitigate oxidative stress-mediated diseases. This study seeks to evaluate the effects of DRLC on memory deficits and the biochemical and histo-morphological changes induced by lipopolysaccharide (LPS) in mice. Male Swiss mice (n = 10) were pre-treated orally with three doses of DRLC (25mg/kg, 50mg/kg, and 100mg/kg), donepezil (1mg/kg), or vehicle (saline) for 30min prior to the intraperitoneal injection of LPS (0.25mg/kg) daily for 7days. Memory functions were evaluated using the Y-maze, object recognition, and social recognition tests. The specific brain regions (prefrontal cortex and hippocampus) were evaluated to determine oxidative stress biomarkers (malondialdehyde, GSH, and catalase), acetyl-cholinesterase activity, proinflammatory cytokines (tumor necrosis factor-α and interleukin-6), expression of nuclear factor-kappa B (NF-κB), and neuronal cell morphology. DRLC (25-100mg/kg) reversed the memory deficits in the LPS-treated mice (p < 0.05). The increased oxidative stress and proinflammatory cytokines in the brain regions of the LPS-treated mice were significantly (p < 0.05) reduced by DRLC. DRLC (50mg/kg and 100mg/kg) also reduced acetyl-cholinesterase activity and decreased NF-κB expression in the brains of LPS-treated mice. Finally, it attenuated the cytoarchitectural distortions and loss of neuronal cells of the prefrontal cortex and hippocampus that were induced by LPS in mice. The results of this study suggest that DRLC attenuates memory deficit induced by LPS in mice through mechanisms related to the inhibition of oxidative stress, release of proinflammatory cytokines, and expression of NF-κB in mice.

Involvement of Cholinergic and Redox Impairments in Insecticidal Properties of Essential Oils from Fertility Tree and Horseradish Tree Leaves in Fruit Fly (Drosophila melanogaster).

This study reports the biological activity of essential oils from fertility tree and horseradish tree leaves, and the mechanisms by which these oils promote insecticidal activity using Drosophila melanogaster as a model organism. Adult D. melanogaster were exposed to these essential oils at a final concentration of 10 µL/g for 24 hours. The exposure of flies to the essential oil resulted in significant decrease in their survival and fecundity. In addition, the essential oils produced significant reduction in acetylcholinesterase activity and induced oxidative stress in the flies as evidenced by an increase in reactive oxygen species, thiol and thiobarbituric reactive substance levels, as well as catalase activity. The essential oils were also characterized by gas chromatography coupled with mass spectrometry. Constituents such as terpenoids, Bis (2-ethylhexyl) phthalate, benzeneacetaldehyde, phytol, octadecane, 9,12-octadecadienoic acid (Z,Z)- methyl ester, heneicosane, eicosane and others were characterized. Therefore, our results point out to the potential application of fertility tree and horseradish tree leaf essential oils as natural alternatives to synthetic insecticides in agricultural and pest control practices, especially against dipterans.

Methyl jasmonate abrogates rotenone-induced parkinsonian-like symptoms through inhibition of oxidative stress, release of pro-inflammatory cytokines, and down-regulation of immnopositive cells of NF-κB and α-synuclein expressions in mice

Oxidative stress and neuroinflammation play key roles in the initiation and progression of Parkinson's disease (PD), a neurodegenerative disorder, associated with the loss of nigrostriatal dopaminergic pathway. Thus, compounds that can mitigate oxidative stress and neuroinflammation are being investigated as promising agents for the treatment of PD. This study was designed to evaluate the effects of methyl jasmonate (MJ), a potent antioxidant and anti-inflammatory compound on parkinsonian-like symptoms and the underlying biochemical changes induced by rotenone (Rot) in mice. To this end, the effects of graded doses of MJ (25, 50 and100 mg/kg, i.p.) on motor dysfunctions, cognitive and depressive-like disorders induced by Rot (2.5 mg/kg, i.p.) were evaluated. The specific brain regions (striatum, prefrontal cortex and hippocampus) of the animals were processed for various biochemical studies. Rot-treated mice showed reduced motor activity, postural instability, cognitive and depressive-like disorders. Rot also increased brain levels of malondialdehyde (MDA), nitrite, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and acetyl-cholinesterase (AChE) activity. Moreover, Rot reduced the concentration of glutathione (GSH) and increased immnopositive cells of NF-κB and α-synuclein expressions in these brain regions. However, pretreatment with MJ, attenuated the parkinsonian-like symptoms and reduced the brain levels of MDA/nitrite, TNF-α and IL-6 induced by Rot. MJ also reduced AChE activity and down-regulate the expressions of NF-κB and α-synuclein in the brain of Rot-treated mice. These findings suggest that MJ has anti-parkinsonian-like activity, which may be related to the inhibition of oxidative stress, release of pro-inflammatory cytokines, and down regulation of NF-κB and α-synuclein expressions.

Potent Acetylcholinesterase Selective and Reversible Homodimeric Agent Based on Tacrine for Theranostics.

Acetylcholinesterase (AChE) has been an important biomarker for diagnosing Alzheimer's disease (AD), due to reduction in AChE activity in post-mortem brains of AD patients. A potent, selective, and reversible homodimeric inhibitor of AChE, 5-amino- N1, N3-bis(2-(1,2,3,4-tetrahydroacridin-9-ylamino)ethyl)isophthalamide (compound 4), was synthesized by using 9-alkyl(1,2,3,4-tetrahydroacridine) pharmacophore with appended functionality. In the present work, we report the synthesis of this bivalent inhibitor of AChE. The homodimeric ligand structure was designed and studied with molecular docking tools, which revealed its high affinity and interactions with active site gorge of AChE, which includes both catalytic active site (CAS) and peripheral active site (PAS). The IC50 value of this bivalent inhibitor for AChE and BuChE were 0.54 ± 0.06 and 32.49 ± 1.2 nM, respectively, with a selectivity ratio of 60.16 toward AChE. The designed ligand also showed potent inhibitory properties on PAS activity as well as on AChE-induced amyloid aggregation with low cytotoxicity on rat hippocampal neurons. The AFM images further corroborated the Aβ1-42 aggregation inhibition by compound 4 to an extent similar to bis(7)-tacrine. Moreover, the bivalent ligand was also proven to be of neurogenic potential due to its ability to induce S-phase post-treatment in rat hippocampal neuronal cells. On the basis of initial results, the agent could be further explored for its theranostic value clinically, which gives the possibility of tracing the AChE levels by molecular imaging techniques in correlation with progression of neurocognitive disorders like AD for better therapy response and patient management.

Organochlorine and organophosphorus pesticides and bladder cancer: A case-control study.

Exposure to pesticides is associated with an increase in the incidence of cancer. We aimed to investigate the association of serum organochlorine pesticides (OCPs) and organophosphorus pesticides (OPs) levels and GSTM1/GSTT1 gene polymorphism with bladder cancer (BC). This study was performed on 57 patients with BC and 30 controls (C). Acetylcholinesterase (AChE) activity, arylesterase activity of paraoxonase-1 (ARE), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were determined in serums of all participants. Genomic DNA was extracted using the salting out method and GSTM1/GSTT1 gene polymorphisms were examined by multiplex polymerase chain reaction assay. Measurement of OCPs (α-hexachlorocyclohexane [α-HCH], β-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane [2,4-DDT], 4,4-DDT, 2,4- dichlorodiphenyldichloroethylene [2,4-DDE], and 4,4-DDE) in serum was carried out using an FID-equipped gas-chromatography system. AChE activity was significantly lower, ARE activityand TAC were declined but it was not statistically significant, however, α-HCH, γ-HCH, 4,4-DDE, 2,4-DDT, and 4,4-DDT pesticides, and MDA were significantly higher in BC patients compared with the control subjects. Also, a positive correlation was found between the number of smoked cigarettes and the years of smoking with BC development. There was no association between GSTM1/GSTT1 gene polymorphisms and OCPs in BC patients. Due to the higher levels of some OCPs in the BC patients, along with the reduction in AChE activity and increased MDA levels, it may be concluded that OCPs and OPs play an important role in the induction of BC in southeastern Iran.

Novel compound VB-037 inhibits Aβ aggregation and promotes neurite outgrowth through enhancement of HSP27 and reduction of P38 and JNK-mediated inflammation in cell models for Alzheimer's disease

The pathogenesis of Alzheimer's disease (AD) is involved in the aggregation of misfolded amyloid β (Aβ), which upregulates the activity of acetylcholinesterase (AChE), increases the production of reactive oxygen species (ROS), enhances neuroinflammation, and eventually leads to neuronal death. Therefore, compounds targeting these mechanisms may be candidates for multitarget drugs in AD treatment. We found that two quinoline derivatives, VB-030 and VB-037, markedly reduced Aβ aggregation and ROS levels in the thioflavin T biochemical assay and Tet-On Aβ-green fluorescent protein (GFP) 293 AD cell model. These compounds further improved neurite outgrowth, reduced AChE activity and upregulated the molecular chaperone heat shock protein family B [small] member 1 (HSP27), whereas knockdown of HSP27 counteracted the compounds' neuroprotective effects on the Tet-On Aβ-GFP SH-SY5Y AD neuronal model. Furthermore, VB-037 attenuated lipopolysaccharide (LPS)/interferon (IFN)-γ-induced activation of BV-2 microglial cells. In addition, VB-037 demonstrated its potential to diminish LPS/IFN-γ-induced upregulation of caspase 1 activity, expression of interleukin (IL)-1β, and active phosphorylation of mitogen-activated protein kinase 14 (P38), mitogen-activated protein kinase 8 (JNK), and Jun proto-oncogene, AP-1 transcription factor subunit (JUN) signalings, as well as improve cell viability in the Tet-On Aβ-GFP SH-SY5Y AD neuronal model. Our findings strongly indicate the potential of VB-037 for modifying AD progression by targeting multiple mechanisms, thereby offering a new drug development avenue for AD treatment.

Antioxidative status, immunological responses, and heat shock protein expression in hepatopancreas of Chinese mitten crab, Eriocheir sinensis under the exposure of glyphosate

As a broad-spectrum herbicide, glyphosate was extensively utilised in China for several decades. The contradiction between glyphosate spraying and crab breeding in the rice-crab co-culture system has become more obvious. In this study, the antioxidative status and immunological responses of Chinese mitten crab, Eriocheir sinensis, under sublethal exposure of glyphosate were investigated by detecting the antioxidative and immune-related enzyme activity, acetylcholinesterase (AChE) activity and relative mRNA expression of heat shock proteins (HSPs) in hepatopancreas. The results showed that high concentrations of glyphosate (44 and 98 mg/L) could induce significant alteration of superoxide dismutase (SOD), peroxidase (POD), acid phosphatase (ACP), alkaline phosphatase (AKP), and phenoloxidase (PO) activities by first rising then falling during the exposure. However, AChE activity in all treatments including 4.4 mg/L was inhibited markedly after 6 h of exposure. In addition, the relative mRNA expression of HSP 60, HSP 70, and HSP 90 was significantly upregulated at both 48 h and 96 h. These results revealed that glyphosate has a prominent toxic effect on E. sinensis based on antioxidative and immunological response inhibition and AChE activity reduction even at the lowest concentration of 4.4 mg/L, and a protective response by upregulation of HSPs was carried out by the species to ease the environmental stress.

Metabolic treatment of syndrome linked with Parkinson's disease and hypothalamus pituitary gonadal hormones by turmeric curcumin in Bisphenol-A induced neuro-testicular dysfunction of wistar rat

The metabolic shift in cholinesterase activity and inhibitor of hypothalamus pituitary gonadal hormones were hypothesized as resultant effect of Parkinson's disease (PD) which is clinically characterized by a movement disorder. This study therefore examined the effect of turmeric curcumin (CUR) on index of PD, acetylcholine esterase activity and disorder of hypothalamus pituitary gonadal hormone (HPGH) in Bisphenol-A induced injury using animal model. Forty adult male albino rats were randomly distributed into five (n = 8) groups. Group I: vehicle control (olive oil 0.5 ml), Group II was given 50 mg/kg of BPA only, Group III was given 50 mg/kg BPA + 50 mg/kg curcumin, Group IV was given 50 mg/kg BPA + 100 mg/kg curcumin and Group V was administered 50 mg/kg of curcumin only for 14 days. The study examined the effect of curcumin on acetylcholineesterase (AChE) activity, nitric oxide radical (NO•) production, HPGH (LH, FSH and testosterone), MDA level, antioxidant enzymes (SOD and CAT), in BPA induced male rat. Sperm parameters were similarly examined. The animals induced with BPA exhibited impairment to striatum, leydig cells and sertoli cells by depleting LH, FSH, testosterone and spermatozoa with reduced AChE activity and significant (p < 0.05) alteration in cerebral enzymatic antioxidants. Locomotive activity was impeded followed by the increase of brain NO• level (marker of pro-inflammation). Therapeutically, CUR promoted hypothalamus–pituitary–testicular hormones via modulation of AChE and locomotive activities, reduction of intracellular NO• level, prevention of striatum-endocrine injury as well as oxidative damage. Hence, CUR abolished HPGH dysfunction linked with PD mediated by BPA in rat.

Schisanhenol improves learning and memory in scopolamine-treated mice by reducing acetylcholinesterase activity and attenuating oxidative damage through SIRT1-PGC-1α-Tau signaling pathway

Purpose: Schisanhenol is a compound derived from the fruit of a traditional Chinese herb Schisandra rubriflora. The aim of the present study was to evaluate the effect of Schisanhenol on the cognitive impairment induced by scopolamine.Material and Methods: Male mice were randomly divided into three Schisanhenol groups (10, 30, 100 mg/kg), Galantamine group (3 mg/kg), model group (1mg/kg scopolamine), and vehicle control group (normal saline). The learning and memory ability of mice was monitored by water morris maze. Hippocampus of mice were collected after behavioral testing and the activity of SOD, MDA, GSH-px, AChE were measured with standard biochemical procedures. Western blotting was used to analyze the expression of SIRT1, PGC-1α, phosphorylated Tau proteins.Results: Intraperitoneal administration of Schisanhenol (10, 30 or 100 mg/kg) significantly attenuated scopolamine-induced cognitive impairment in water morris maze. In addition, Schisanhenol increased the activity of SOD and GSH-px while decreased the content of AChE and MDA. Furthermore, western blotting analysis revealed that Schisanhenol increased the levels of SIRT1 and PGC-1α and decreased the level of phosphorylated Tau protein (Ser 396) significantly in the hippocampal tissues.Conclusions: Our findings indicated that Schisanhenol can attenuate scopolamine-induced learning impairment and enhance cognitive function, the mechanism via improve the cholinergic system and antioxidant ability, activate SIRT1-PGC1α signaling, inhibit the phosphorylation of Tau, and would be an effective candidate against cognitive disorders, such as Alzheimer's disease.

Constant exposure to environmental concentrations of the antifouling biocide Sea-Nine retards growth and reduces acetylcholinesterase activity in a marine mysid

Sea-Nine (4,5-dichloro-2-n-octyl-4-isothiazoline3-one; DCOIT) antifoulant has been widely used owing to its broad spectrum of biocide activity against major fouling organisms. In this study, several physiological parameters of a marine mysid were analyzed upon exposure to sublethal environmental concentrations (1 and 100 ng L−1) of Sea-Nine in two exposure conditions, intermittent (weekly; once per week) and constant (daily; once per 24 h) exposure, for 4 weeks. In both experimental conditions, growth retardation, acetylcholinesterase (AChE) activity, glutathione S-transferase (GST) activity, and number of newborn juveniles as second generation, together with their survival were measured. Morphometric parameters of total body, antennal scale, exopod, endopod, and telson were significantly retarded by 22%, 14%, 13%, and 24%, respectively, by daily exposure to 100 ng L−1 Sea-Nine for 4 weeks. Significant inhibition of AChE activity was observed at week 4 in the 100 ng L−1 daily Sea-Nine-exposed groups, whereas no significant GST activity was measured at the same experimental conditions. Inhibition of AChE activity would be associated with impairment of cholinergic system and may adversely modulate growth parameters of the mysid. The number of newly hatched juveniles from females that were exposed daily to 100 ng L−1 Sea-Nine was significantly lower than that of the control. Although no significant differences were observed between survival percentages of newborn juveniles for 30 days, mortality (NOEC and LC50) increased in the surviving offspring from the 100 ng L−1-exposed 1st generation of mysids. These findings suggested that constant exposure to Sea-Nine has detrimental effects on the growth parameters of marine mysids with inhibition of AChE activity.

Inhibition of Nicotine Dependence by Curcuminoid Is Associated with Reduced Acetylcholinesterase Activity in the Mouse Brain

Nicotine is a stimulatory component in tobacco that activates the central nervous system reward pathway and causes nicotine dependence. We found that the anti-inflammatory agent, curcuminoid, prevents nicotine dependence and relapse, as assessed by the conditioned placed preference test. Curcuminoid (1, 3.2, and 10 mg·kg^–1, oral) dose-dependently inhibited nicotine dependence and enhanced nicotine extinction when administrated 30 min prior to nicotine administration (0.5 mg·kg^–1, i.p.) for 7 days. In addition, curcuminoid significantly suppressed the priming effects of nicotine and inhibited acetylcholinesterase (AChE) activity. Taken together, curcuminoid ameliorates nicotine dependence and relapse, in part via the inhibition of the AChE activity in the brain.

Functional Drink Containing the Extracts of Purple Corn Cob and Pandan Leaves, the Novel Cognitive Enhancer, Increases Spatial Memory and Hippocampal Neuron Density Through the Improvement of Extracellular Signal Regulated Protein Kinase Expression, Cholinergic Function, and Oxidative Status in Ovariectomized Rats.

Due to requirement of novel memory enhancer for menopausal women, this study aimed to determine safety and effect of the functional drink containing the extracts of purple corn cob and pandan leaves (PCP) on memory and brain changes in experimental menopause induced by bilateral ovariectomy (OVX). Acute toxicity of PCP was carried out in female Wistar rats. The results showed that LD50 was more than 2000 mg/kg BW. To determine the cognitive enhancing effect of PCP, OVX rats were orally treated with PCP at the doses of 20, 40, and 80 mg/kg BW for 28 days. The spatial memory was assessed every 7 days throughout the study period. At the end of the study, oxidative stress status, acetylcholinesterase (AChE) activity, monoamine oxidase (MAO) activity, neuronal density, and extracellular signal regulated protein kinase 1 and 2 (ERK1/2) signaling in hippocampus were measured. The improved spatial memory, ERK1/2 expression, and neuron density in dentate gyrus of hippocampus were observed in PCP-treated rats. In addition, a reduction of AChE activity was also observed. Unfortunately, no improved oxidative stress status was observed. Taken altogether, PCP exerts the memory-enhancing effect partly through the suppression of AChE and the increase in ERK signaling in the hippocampus.