Cerebral Acetylcholinesterase Research Articles

Protective effects of gestational folic acid and egg yolk powder solution intubation on motor coordination, anxiety, cognition, acetylcholinesterase activity and DNA fragmentation in prenatal alcohol exposed rats

AbstractBackgroundDevelopment of neurobehavioural disorders can occur in the postnatal life of foetuses prenatally exposed to alcohol, regardless of the alcohol type consumed during pregnancy. Hence, the need to investigate the efficacy of proposed pharmaco‐nutritional therapy in mediating potential behavioural and cholinergic impairments in prenatal alcohol exposed (PAE) fetuses.MethodWe investigated whether PAE exacerbates anxiety, motor coordination, cognitive function, cerebral cortex acetylcholinesterase (ACh) activity, DNA fragmentation and assessed associations among parental and PAE rats’ cerebral cortex ACh activity. Thirty female Wistar rats were mated in the following groups (n = 6): 1: Negative control (distilled water only), 2: Positive control (40% EtOH), 3: local gin (LG), 4: local gin+egg yolk solution(LGEY) 5: local gin +egg yolk solution+folic acid(LGEYFA). Statistical significance of obtained data was measured at p<0.05 using regression model, ANOVA and Tukey’s PostHoc tests (GraphPad 5).ResultWhen compared to the negative control, all alcohol groups (supplemented or not) had significantly lower latency of fall, working memory, percentage alternation etc. Although the brain weight of PAE rats in group 2 (positive control) did not change significantly (p = 0.159), critically reduced brain weights seen in group 3 (LG, p<0.001) were normalized in the supplemented groups (4‐LGEY and 5‐LGE). Cortex protein levels was unchanged in all maternal rats regardless of alcohol intubation. However, ACh cerebral cortex activity was significantly reduced in PAE rats from non‐supplemented groups (2 and 3). Necrosis and fragmentation were also seen in agarose gel electrophoregram (AGE) of gDNA isolated from PAE rats’ brain.ConclusionPrenatal alcohol exposure predisposes to severe neurobehavioural and cognitive deficits while gestational folic acid+egg yolk solution may be a therapeutic target for high risk PAE pregnancies.

From carrion-eaters to plastic material plunderers: Toxicological impacts of plastic ingestion on black vultures, Coragyps atratus (Cathartiformes: Cathartidae)

Despite plastic ingestion has already been reported in several bird species, its physiological impacts have been little inspected, especially in representatives of the Cathartidae family. Thus, in this study, we aimed to identify, characterize, and evaluate the effects arising from the ingestion of plastic materials by Coragyps atratus adults, that captured in landfill areas. Herein, a total of 51 individuals were captured, the frequency of plastic intake being higher than 40%. The plastic materials consisted mainly of low-density polyethylene and film-type polystyrene, as well as presenting irregular shapes and diameters between 10 and 30 mm. Biochemically, we observed in animals that contained plastics in the stomach ("plastic" group) high production of reactive oxygen species (ROS), hydrogen peroxide (H2O2) and malondialdehyde (MDA) - especially in the intestine, muscle and brain - whose activity of catalase (CAT) and superoxide dismutase (SOD) was not sufficient to counteract the oxidative stress. Moreover, in the liver of these same animals, we observed high production of nitrite and nitrate, suggesting a hepatic nitrosative stress. Plus, we observed a cholinesterase effect in animals from the “plastic” group, marked by increased activity of butyrylcholinesterase (BChE) (in the brain) and muscle and cerebral acetylcholinesterase (AChE). On the other hand, the biochemical changes perceived were not significantly correlated with the identified plastic material concentrations (2.808 ± 0.598 items/g of stomach content and 0.276 ± 0.070 items/g of stomach – fresh weight), body condition of the animals, size, and shape of the identified plastic materials. Hence, our study sheds the light on the toxicity of plastics deposited in landfills and their ingestion by C. atratus, which reinforces the hypothesis that these materials are harming the health of these birds and, consequently, the dynamics of their populations.

Cotreatment of Small Gold Nanoparticles Protects Against the Increase in Cerebral Acetylcholinesterase Activity and Oxidative Stress Induced by Acute Ethanol Exposure in the Zebrafish

Gold nanoparticles (GNP) have emerged as an alternative to biomaterials in biomedical applications. Research has clearly demonstrated the relative safety and low toxicity of these molecules. However, the possible neuroprotective effect of GNP on the central nervous system (CNS) and its relationship with neurological and psychiatric disorders remain unclear. Zebrafish is a reliable model to investigate the impact of ethanol (EtOH) consumption on the CNS, including reward signaling such as the cholinergic neurotransmission system. Here, we investigated whether cotreatment or pretreatment with GNP prevented EtOH-induced changes in acetylcholinesterase activity and oxidative stress in the brain of zebrafish. We exposed adult zebrafish to 2.5 mg·L−1 GNP 1 h prior to EtOH (1% v/v) treatment for 1 h, and cotreated adult zebrafish simultaneously with both substances for 1 h. Pretreatment with GNP did not prevent EtOH-induced increase in the acetylcholinesterase activity, whereas cotreatment with 2.5 mg·L−1 GNP and EtOH protected against this increase. The results also suggested similar protective effect on oxidative stress parameters in the zebrafish pretreated with GNP at 2.5 mg·L−1. GNP significantly decreased the levels of thiobarbituric acid reactive species and dihydrodichlorofluorescein levels when cotreated with EtOH. GNP also prevented EtOH-induced increase in superoxide dismutase and catalase activities, suggesting a modulatory role of GNP in enzymatic antioxidant defenses. Our results showed that GNP was able to modulate the disruption of cholinergic and oxidative homeostasis in the brain of zebrafish. These findings indicate for the first time that zebrafish is an interesting perspective to investigate nanoparticles against disorders related to alcohol abuse.

Red-to-blue paper-based colorimetric sensor integrated with smartphone for point-of-use analysis of cerebral AChE upon Cd2+ exposure.

Herein, combined with a pervasive smartphone installed with a color recognition app, dual-responsive CDs@Eu/GMP ICPs were designed as a red-to-blue paper-based colorimetric sensor for the point-of-use analysis of cerebral acetylcholinesterase (AChE) upon Cd2+ exposure. Blue-emitting CDs with multi-functional groups as guests were encapsulated into the network of Eu/GMP ICPs to obtain CDs@Eu/GMP ICPs with the sensitized red fluorescence of Eu3+. With the presence of thiocholine (TCh), derived from acetylthiocholine (ATCh) hydrolyzed by AChE, the coordination environment of the CDs@Eu/GMP ICPs was interrupted, leading to the collapse of the CDs@Eu/GMP ICP network and the corresponding release of guest CDs into the surrounding environment. Consequently, the sensitized red fluorescence of Eu3+ decreased and the blue fluorescence of the CDs increased. This obvious red-to-blue fluorescent color changes of CDs@Eu/GMP ICPs on test paper could then be integrated with the smartphone for point-of-use analysis of cerebral AChE upon Cd2+ exposure, which not only offers a new analytical platform for a better understanding of the environmental risk of Alzheimer's Dementia (AD), but also holds great potential in the early diagnosis of AD even at the asymptomatic stage with the decrease in CSF AChE as an early biomarker.

In vivo cholinesterase sensitivity of gilthead seabream (Sparus aurata) exposed to organophosphate compounds: Influence of biological factors

Two cholinesterases have been found in vertebrates, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes are present in the gilthead seabream, AChE in the brain and muscle and BChE in the muscle. Cholinesterases have been used as biomarker of effect in environmental monitoring studies. However, there are few studies about the influence of biometric parameters on ChE. This paper studies the possible influence of biological factors on brain and muscle cholinesterase (ChE) in Sparus aurata. Our results show that ChE activity in brain and muscle tissues changes depending on several biological variables. ChE activity in these tissues decreased when the age (48–152 week), body length (14.15–28.95 cm) and body weight (42.73–380.74 g) of the fishes studied increased. The relationships between brain and muscle ChE activity and several biometric factors were curvilinear.On the other hand, in vivo sensitivity of cholinesterase in the gilthead seabream exposed to organophosphorus pesticides (azinphosmethyl, dimethoate and dichlorvos) was studied in order to learn about recovery from cholinesterase present (brain and muscle) after exposure to a sublethal dose. The recovery of muscle AChE was similar to cerebral AChE, while muscular BChE showed a slower recovery.

Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin.

In the scope of the study, the protective effect of hesperidin (HES), a flavanone glycoside, was investigated against sodium arsenite (NaAsO2, SA) induced heart and brain toxicity. For this purpose, 35 Sprague-Dawley male rats were divided into 5 different groups, 7 in each group. Physiological saline was given to the first group. Dose of 200 mg/kg of HES to the second group, 10 mg/kg dose of SA to the 3rd group, 100 mg/kg HES and 10 mg/kg SA to the 4th group, 200 mg/kg HES, and 10 mg/kg SA to the 5th group were given orally for 15 days. At the end of the study, biochemical, histopathological, and immunohistochemical examinations were performed on the heart and brain tissues of the rats. According to the results, SA increased malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and decreased glutathione (reduced, GSH) level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in both tissues. Also, it increased cardiac lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CK-MB) activities and cardiac troponin-I level (cTn-I), cerebral acetylcholine esterase activity, nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), and cysteine aspartate-specific protease-3 (caspase-3) levels. In addition, as a result of histopathological examination, it was determined that SA damaged tissue architecture, and as a result of immunohistochemical examination, it increased cardiac Bcl-2-associated X protein (Bax) and cerebral glial fibrillary acidic protein (GFAP) expression. The results have also shown that HES co-treatment has an antioxidant, anti-inflammatory, antiapoptotic effect on SA-induced toxicity and aids to protect tissue architecture by showing a regulatory effect on all values. Consequently, it was determined that HES co-treatment had a protective effect on SA-induced heart and brain toxicity in rats.

Behavioral impairment and neurotoxic responses of silver catfish Rhamdia quelen exposed to organophosphate pesticide trichlorfon: Protective effects of diet containing rutin

Trichlorfon is an organophosphate pesticide used extensively for controlling ectoparasites in aquaculture. Studies have found that trichlorfon caused environmental pollution and severe neurotoxic effects in several freshwater species. Feed additives such as flavonoids may reduce or prevent pesticide-induced toxicity in fish. The aim of the present study was to determine whether acute exposure to trichlorfon impairs behavior and causes oxidative damage in brains of silver catfish (Rhamdia quelen). We also sought to determine whether rutin would be capable of preventing or reducing these effects. Silver catfish were divided into four groups: groups A and C received basal feed, while groups B and D received feed containing 3 mg rutin/kg diet for 21 days. After 21 days, groups C and D were exposed for 48 h to a nominal concentration of 11 mg trichlorfon/L water. Fish exposed to trichlorfon showed significantly longer distances travelled and swimming performances than did unexposed fish. Cerebral levels of reactive oxygen species and lipid peroxidation were significantly higher in fish exposed to trichlorfon than in unexposed fish, while cerebral superoxide dismutase, catalase, glutathione peroxidase, and acetylcholinesterase (AChE) activities were significantly lower. Taken together, our findings suggest that dietary supplementation rutin completely prevented all alterations elicited by trichlorfon, except for cerebral AChE activity; the latter remained significantly lower compared to the unexposed group. In summary, rutin prevents trichlorfon-induced neurotoxicity in silver catfish.

Toxicological effects of anthropogenic activities in Geophagus brasiliensis from a coastal river of southern Brazil: A biomarker approach

This study aimed to assess the water quality of the Perequê River, Porto Belo, Santa Catarina, Brazil, through a biomarker approach in the native fish species Geophagus brasiliensis, and the sediment chemical quantification of the herbicides glyphosate and bentazone used in irrigated rice plantations. This river is used for the public water supply of two municipalities. The first sampling (S1) was in November 2016, in the spring season and the second (S2), in March 2017, in the fall season. In each sampling, two points of the river were analyzed, one upstream of the accumulation dam and the water catchment point for water supply of the Porto Belo WTS (P1), and another downstream (P2) with water, sediment, and fish sampling. Biotransformation, oxidative stress, histopathological and genotoxic biomarkers were analyzed in different tissues. The presence of glyphosate was detected in the sediment (11.7 μg·kg−1) from the upstream point of the water catchment site (P1) in spring. The lower activity of the antioxidant enzyme superoxide dismutase (SOD), as well as the increased damage to renal DNA and hepatic tissue, coincided with the lower muscular and cerebral acetylcholinesterase activities (AChE) at P1, in relation to P2 in the spring season, with a lower rainfall index (81.8 mm3). A seasonal variation was also observed between the spring and fall seasons, in fish responses to biomarkers. Reduction of muscle AChE activity and biotransformation enzymes ethoxyresorufin-O-deethylase and glutathione S-transferase and antioxidant enzymes such as, SOD and glutathione peroxidase, as well as increased brain DNA damage, coincided with the highest number of tissue lesions in the liver and gills in the spring, regardless of the sampling point. The results suggested that the Perequê River is contaminated by xenobiotics and probably herbicides from irrigated rice plantations, indicating damages to the biota and a potential public health risk.

Fish exposed to water contaminated with eprinomectin show inhibition of the activities of AChE and Na+/K+-ATPase in the brain, and changes in natural behavior

The objective of this study was to evaluate whether antiparasitic eprinomectin may be an environmental contaminant in water compartment in low concentrations, negatively affecting neurotransmission and, consequently, the natural behavior of the jundiá (Rhamdia quelen). Fish were randomly allocated in tanks and exposed for 24 and 48 h to eprinomectin concentrations in water [0.0 (Control), 1.124 (T1), 1.809 (T2) and 3.976 (T3) μg L−1], followed by 48 h of recovery in eprinomectin-free water, in order to evaluate the behavioral parameters, levels of reactive oxygen species (ROS) in the brain, as well as cerebral enzymatic activities of acetylcholinesterase (AChE) and of the sodium-potassium ATPase pump (Na+/K+-ATPase). Especially at the two highest concentrations of eprinomectin (T2 and T3), the fish showed alterations in natural behavior, particularly hyperlocomotion and longer time on the surface. Furthermore, at these same concentrations, cerebral ROS levels increased and cerebral AChE activity decreased. At the highest concentration (T3) cerebral Na+/K+-ATPase activity was reduced. Increased ROS and impairment of AChE and Na+/K+-ATPase enzymes in the brain may have contributed directly to behavioral changes, due to neuronal damage and synapse impairment. Even after 48 h in water without eprinomectin, behavioral changes and neurotoxic effects were observed in fish, suggesting residual effects of the antiparasitic. In conclusion, eprinomectin even in low concentrations may be a hazardous environmental contaminant for aquatic organisms, as it causes brain damage and affects the natural behavior of fish.

The acute and chronic effect of Roundup herbicide on histopathology and enzymatic antioxidant system of Oncorhynchus mykiss

Unconventional and uncontrolled use of agricultural pesticides and their influence in aquatic ecosystems during drainage process causes the accumulation of these toxins in body tissues of fish, and finally, it endangers human health. In order to determine the amount of pollution of Roundup pesticide in aquatics, acute and chronic effects of this poison on gill, kidney, and liver tissues and biochemical activities of cerebral acetyl cholinesterase and liver catalase in rainbow trout (Oncorhynchus mykiss) were investigated. To determine LC50 of Roundup pesticide in rainbow trout, acute doses of Roundup were introduced to fish tanks and fish mortality was recorded for 96 h, and Roundup LC50 was determined using SPSS Probit test. Chronic doses were determined based on the obtained LC50, and the effects of these concentrations were assessed on gill, kidney and liver tissues and cerebral acetyl cholinesterase and liver catalase activities over 28 days. Based on histopathology results, the following changes were observed: adhesion of secondary lamellae, bending of secondary lamellae in gill tissue, glomerular wrinkling, dilatation of Bowman’s capsule space in kidney tissue and necrosis, cellular swelling, and lipid degeneration in liver tissue. Cerebral acetyl cholinesterase and liver catalase activities significantly reduced in groups exposed to Roundup herbicide compared to the control group (p < 0.05). Generally, chronic concentrations of Roundup herbicide cause undesirable tissue and enzymatic changes in antioxidant system of rainbow trout. Therefore, assessment of biochemical factors and histopathological studies can be used as biomarkers in tracing the effects of agricultural toxins on aquatic habitat.

Na+/K+-ATPase, acetylcholinesterase and glutathione S-transferase activities as new markers of postmortem interval in Swiss mice.

Determining precisely the postmortem interval (PMI) is a key parameter for forensic researches, given that various physical, biochemical and metabolic changes begin to occur in the body after death. In the present study, the Na+/K+-ATPase, glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities were evaluated. For this, male adult Swiss mice were killed by isoflurane inhalation anesthesia and divided into four groups according to time of death (0, 6, 24 and 48 h). The brain, liver, kidney and skeletal muscle tissues were removed. Our results revealed that at the time of 6 h, there was a decrease on Na+/K+-ATPase and GST activities in the brain and liver tissues, respectively. In addition, at this time point, an increase on renal GST activity was verified. At the time of 24 h, an increase on the cerebral AChE and renal GST activities was observed, while the cerebral Na+/K+-ATPase activity was decreased. Forty-eight hours after death, cerebral Na+/K+-ATPase and renal GST activities remained decreased and increased, respectively. In addition, no alteration was observed on the GST activity in the skeletal muscle and brain (in PMIs evaluated). The present study revealed that the brain and kidney (at the times of 24 and 48 h) were the tissues that suffered the most changes in almost all the enzymes evaluated. Our results demonstrated that enzyme activity assessments are reliable, easy-to-perform and low-cost determinations, and could be promising postmortem markers.

Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitive decline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimetic medication. The clinical presentations and courses of AD patients may differ by age of onset. The objective of the present study was to illustrate the regional differences of brain acetylcholinesterase (AChE) activity as quantified by N-[11C]methylpiperidinyl-4-acetate ([11C]MP4A) and PET using parametric whole brain analysis and clarify those differences as a function of age. 22 early onset AD (EOAD) with age at onset under 65, the remaining 26 as late onset AD (LOAD), and 16 healthy controls (HC) were enrolled. Voxel-based AChE activity estimation of [11C]MP4A PET images was conducted by arterial input and unconstrained nonlinear least-squares method with subsequent parametrical analyses. Statistical threshold was set as Family Wise Error corrected, p-value <0.05 on cluster-level and cluster extent over 30 voxels. Voxel-based group comparison showed that, compared to HC, both EOAD and LOAD showed cortical AChE decrement in parietal, temporal, and occipital cortices, with wider and stringent cortical involvement in the EOAD group, most prominently demonstrated in the temporal region. There was no significant correlation between age and regional cerebral AChE activity except for a small left superior temporal region in the AD group (Brodmann's area 22, Zmax = 5.13, 396 voxels), whereas no significant cluster was found in the HC counterpart. Difference in cortical cholinergic dysfunction between EOAD and LOAD may shed some light on the cholinomimetic drug efficacy in AD.

Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury: A PET Study

To investigate quantitative positron emission tomography (PET) findings and to study whether the cholinergic function differs between respondents to cholinergic medication versus nonrespondents. Outpatient clinic and university PET imaging center. We studied 17 subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication. Cholinergic function was assessed with [methyl-C] N-methylpiperidyl-4-acetate-PET (C-MP4A-PET), which reflects the activity of the acetylcholinesterase (AChE) enzyme. The subjects were PET scanned twice: without medication and after a 4-week treatment with rivastigmine 1.5 mg twice a day. Regional cerebral AChE activity was measured with PET. At baseline Statistical Parametric Mapping analyses showed significantly lower AChE activity in respondents bilaterally in the frontal cortex as compared with nonrespondents. Region of interest (ROI) analysis revealed that the difference was most pronounced in the lateral frontal cortex (-9.4%, P = .034) and anterior cingulate (-6.0%, P = .049). After rivastigmine treatment, AChE activity was notably lower throughout the cortex in both respondents and nonrespondents, without significant differences between them. Our study suggests that frontal cholinergic dysfunction is associated with the clinical response to cholinergic stimulation in patients with traumatic brain injury.

Relation between acetylcholinesterase and Na+, K+-ATPase activities with impaired memory of mice experimentally infected by Trypanosoma cruzi

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and causes severe cardiac and brain damage, leading to behavioral alterations in humans and animals. However, the mechanisms involved in memory impairment during T. cruzi infection remain unknown. It has long been recognized that the enzymatic activities of acetylcholinesterase (AChE) and Na+, K+-ATPase are linked with memory dysfunction during other trypanosomiasis. Thus, the aim of this study was to evaluate the involvement of cerebral AChE and Na+, K+-ATPase activities in the memory impairment during T. cruzi (Colombian strain) infection. A significant decrease on latency time during the inhibitory avoidance task was observed in animals infected by T. cruzi compared to uninfected animals, findings compatible to memory dysfunction. Moreover, the cerebral AChE activity increased, while the Na+, K+-ATPase decreased in T. cruzi infected compared to uninfected animals. Histopathology revealed mild to moderate multifocal gliosis in the cerebral cortex and light focal meningeal lymphoplasmacytic infiltrate, which may have contributed to memory loss. Based on these evidences, we can conclude that T. cruzi (Colombian strain) causes memory impairment in mice experimentally infected. Moreover, the changes in AChE and Na+, K+-ATPase activities may be considered a mechanism involved in disease pathogenesis.

Curcumin administration suppress acetylcholinesterase gene expression in cadmium treated rats

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes have been reported to exert anticholinesterase potential with limited information on how they regulate acetylcholinesterase (AChE) gene expression. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA gene expression level in cadmium (Cd)-treated rats. Furthermore, in vitro effect of different concentrations of curcumin (1–5μg/mL) on rat cerebral cortex AChE activity was assessed. Animals were divided into six groups (n=6): group 1 serve as control (without Cd) and receive saline/vehicle, group 2 receive saline plus curcumin at 25mg/kg, group 3 receive saline plus curcumin 50mg/kg, group 4 receive Cd plus vehicle, group 5 receive Cd plus curcumin at 25mg/kg and group 6 receive Cd plus curcumin at 50mg/kg. Rats received Cd (2.5mg/kg) and curcumin (25 and 50mg/kg, respectively) by oral gavage for 7days. Acetylcholinesterase activity was measured by Ellman’s method and AChE expression was carried out by a quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assay. We observed that acute administration of Cd increased acetylcholinesterase activity and in addition caused a significant (P<0.05) increase in AChE mRNA levels in whole cerebral cortex when compared to control group. However, co-treatment with curcumin inhibited AChE activity and alters AChE mRNA levels when compared to Cd-treated group. In addition, curcumin inhibits rat cerebral cortex AChE activity in vitro. In conclusion, curcumin exhibit anti-acetylcholinesterase activity and suppressed AChE mRNA gene expression level in Cd exposed rats, thus providing some biochemical and molecular evidence on the therapeutic effect of this turmeric-derived compound in treating neurological disorders including Alzheimer's disease.

Pseudomonas aeruginosa strain PAO1 infection impairs locomotor activity in experimentally infected Rhamdia quelen: Interplay between a stress response and brain neurotransmitters

The aim of this study was to evaluate whether infection by Pseudomonas aeruginosa, an important opportunistic Gram-negative bacterium, causes behavioral alterations in Rhamdia quelen, as well as to investigate the involvement of markers of stress response and brain neurotransmitters in experimentally infected fish. For this, twelve animals were divided in two groups: uninfected (negative control) and experimentally infected animals with P. aeruginosa (positive control), in order to assess the behavioral parameters, plasma cortisol levels, as well as the Na+, K+-ATPase and acetylcholinesterase (AChE) activities. Animals infected with P. aeruginosa presented a behavioral impairment linked with hyperlocomotion. Also, the plasma cortisol and reactive oxygen species (ROS) levels increased in infected fish compared to uninfected ones. Cerebral Na+, K+-ATPase activity decreased in infected animals, while cerebral AChE activity increased compared to uninfected animals. In summary, fish experimentally infected with P. aeruginosa presented behavioral impairments, which are associated with stress and hyperlocomotion. Moreover, the impairment of the cerebral Na+, K+-ATPase pump and cholinergic system may directly contribute to this behavior, since dysfunction in the synapse is promoted, and levels of ACh, an important neurotransmitter involved in several behavioral functions, is decreased.

White matter lesions and the cholinergic deficit in aging and mild cognitive impairment

In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [11C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants. Only periventricular, not nonperiventricular, WML load negatively correlated with AChE activity in both groups. Memory performance depended on periventricular and total WML load across groups. Crucially, AChE activity predicted memory function better than WML load, gray matter atrophy, or age. The effects of WML load on memory were fully mediated by AChE activity. Data suggest that the contribution of WML to the dysfunction of the cholinergic system in MCI due to AD depends on WML distribution. Pharmacologic studies are warranted to explore whether this influences the response to cholinergic treatment.

Curcumin improves episodic memory in cadmium induced memory impairment through inhibition of acetylcholinesterase and adenosine deaminase activities in a rat model.

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes has been reported to exert cognitive enhancing potential with limited scientific basis. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in cadmium (Cd)-induced memory impairment in rats. Animals were divided into six groups (n=6): saline/vehicle, saline/curcumin 12.5mg/kg, saline/curcumin 25mg/kg, Cd/vehicle, Cd/curcumin 12.5mg/kg, and Cd/curcumin 25mg/kg. Rats received Cd (2.5mg/kg) and curcumin (12.5 and 25mg/kg, respectively) by gavage for 7days. The results of this study revealed that cerebral cortex AChE and ADA activities were increased in Cd-poisoned rats, and curcumin co-treatment reversed these activities to the control levels. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfuhydryl (-SH) group and nitric oxide (NO), a potent neurotransmitter and neuromodulatory agent. However, the co-treatment with curcumin at 12.5 and 25mg/kg, respectively increased the non-enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level. Therefore, inhibition of AChE and ADA activities as well as increased antioxidant status by curcumin in Cd-induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties.

Copper acutely impairs behavioral function and muscle acetylcholinesterase activity in zebrafish (Danio rerio)

Copper is a heavy metal found at relatively high concentrations in surface waters around the world. Copper is a micronutrient at low concentrations and is essential to several organisms. At higher concentrations copper can become toxic, which reveal the importance of studying the toxic effects of this metal on the aquatic life. Thus, the objective of this study was to evaluate the toxic effects of copper on the behavior and biochemical parameters of zebrafish (Danio rerio). Zebrafish were exposed for 24h at a concentration of 0.006mg/L Cu. After the exposure period, behavioral profile of animals was recorded through 6min using two different apparatuses tests: the Novel Tank and the Light–Dark test. After behavioral testing, animals were euthanized with a solution of 250mg/L of tricaine (MS-222). Brain, muscle, liver and gills were extracted for analysis of parameters related to oxidative stress and accumulation of copper in these tissues. Acetylcholinesterase (AChE) activity was determined in brain and muscle. Results showed acute exposure to copper induces significant changes in behavioral profile of zebrafish by changing locomotion and natural tendency to avoid brightly lit area. On the other hand, there were no significant effects on parameters related to oxidative stress. AChE activity decreased significantly in zebrafish muscle, but there were no significant changes in cerebral AChE activity. Copper levels in tissues did not increase significantly compared to the controls. Taken together, these results indicate that a low concentration of copper can acutely affect behavioral profile of adult zebrafish which could be partially related to an inhibition on muscle AChE activity. These results reinforce the need of additional tests to establishment of safe copper concentrations to aquatic organisms and the importance of behavioral parameters in ecotoxicological studies.

Inhibitory Effect of Ebselen on Cerebral Acetylcholinesterase Activity In Vitro: Kinetics and Reversibility of Inhibition

Ebselen is a synthetic organoselenium compound that has been considered a potential pharmacological agent with low toxicity, showing antioxidant, anti-inflammatory and neuroprotective effects. It is bioavailable, blood-brain barrier permeant and safe based on cellular toxicity and Phase I-III clinical trials. There is evidence that ebselen inhibits acetylcholinesterase (AChE) activity, an enzyme that plays a key role in the cholinergic system by hydrolyzing acetylcholine (ACh), in vitro and ex vivo. This system has a well-known relationship with cognitive process, and AChE inhibitors, such as donepezil and galantamine, have been used to treat cognitive deficits, mainly in the Alzheimer's Disease (AD). However, these drugs have poor bioavailability and a number of side effects, including gastrointestinal upsets and hepatotoxicity. In this way, this study aimed to evaluate the effect of ebselen on cerebral AChE activity in vitro and to determine the kinetic profile and the reversibility of inhibition by dialysis. Ebselen inhibited the cerebral AChE activity with an IC50 of 29 µM, similar to IC50 found with pure AChE from electric eel, demonstrating a mixed and reversible inhibition of AChE, since it increased Km and decreased Vmax. The AChE activity was recovered within 60 min of dialysis. Therefore, the use of ebselen as a therapeutic agent for treatment of AD should be considered, although memory behavior tasks are needed to support such hypothesis.