Acetylcholinesterase Activity In Brain Regions Research Articles

Diphenyl diselenide abrogates brain oxidative injury and neurobehavioural deficits associated with pesticide chlorpyrifos exposure in rats

Exposure to pesticide chlorpyrifos (CPF) is associated with neurodevelopmental toxicity both in humans and animals. Diphenyl diselenide (DPDS) is a simple synthetic organoselenium well reported to possess antioxidant, anti-inflammatory and neuroprotective effects. However, there is paucity of information on the beneficial effects of DPDS on CPF-mediated brain injury and neurobehavioural deficits. The present study investigated the neuroprotective mechanism of DPDS in rats sub-chronically treated with CPF alone at 5 mg/kg body weight or orally co-treated with DPDS at 2.5 and 5 mg/kg body weight for 35 consecutive days. Endpoint analyses using video-tracking software in a novel environment revealed that co-treatment with DPDS significantly (p < 0.05) protected against CPF-mediated locomotor and motor deficits precisely the decrease in maximum speed, total distance travelled, body rotation, absolute turn angle, forelimb grip strength as well as the increase in negative geotaxis and incidence of fecal pellets. The enhancement in the neurobehavioral activities of rats co-treated with DPDS was verified by track plot analyses. Besides, DPDS assuaged CPF-induced decrease in acetylcholinesterase and antioxidant enzymes activities and the increase in myeloperoxidase activity and lipid peroxidation level in the mid-brain, cerebral cortex and cerebellum of the rats. Histologically, DPDS co-treatment abrogated CPF-mediated neuronal degeneration in the cerebral cortex, dentate gyrus and cornu ammonis3 in the treated rats. In conclusion, the neuroprotective mechanisms of DPDS is related to the prevention of oxidative stress, enhancement of redox status and acetylcholinesterase activity in brain regions of the rats. DPDS may be a promising chemotherapeutic agent against brain injury resulting from CPF exposure.

Acetylcholinesterase activity in brain regions of rats administered cannabinoids’ extract

Acetylcholinesterase activity in brain regions of rats administered cannabinoids’ extract

Can acetylcholinesterase activity be considered as a reliable biomarker for the assessment of cadmium-induced neurotoxicity?

Gonçalves et al. (2012) recently reported the findings of a long-awaited study on the effects of long-term dietary-induced exposure to cadmium (Cd) on the acetylcholinesterase (AChE) activity of adult rodents' brain regions. Their study can be regarded as a significant contribution to the field, as there is paucity of information on the AChE activity in brain regions following exposure to Cd. However, the Cd-induced modulation of AChE activity is an issue surrounded by controversy. We, herein, discuss and summarize the relative in vivo and in vitro experimental data, and set out to answer the straightforward question: can AChE activity be considered as a reliable biomarker for the assessment of Cd-induced neurotoxicity? At this time, we can not answer in the affirmative because of the variation in techniques used and conclusions reached. We make a plea that authors aiming to explore this potential use of brain AChE activity in the future: (a) are aware of the biases that their experimental approach might exert upon this neurochemical parameter, (b) avoid the use of anaesthesia as a mode of sacrifice and clarify its timing, (c) decide upon the use of previously-studied in vivo experimental schemes (so that they can provide comparable results), and finally, (d) identify pharmacological, biochemical and molecular approaches that are appropriate to clarify the implicated mechanism(s) through which Cd modifies AChE activity.

The effect of acute severe monocrotophos poisoning on inhibition, expression and activity of acetylcholinesterase in different rat brain regions

AimThis study examined the acute effects of severe monocrotophos (MCP) poisoning on AChE inhibition, mRNA expression and recovery of acetylcholinesterase activity in different regions of the rat brain. StudyWistar rats were administered monocrotophos (0.8LD50) by oral gavage to elicit severe effects of acute poisoning and were sacrificed 2.5h, 24h, 7 days, 14 days and 1 month after poisoning. Acetylcholinesterse activity, mRNA and protein were assessed in cortex, striatum, hippocampus and cerebellum. ResultsAcute monocrotophos administration resulted in significant AChE inhibition (50–82%) in the rat brain regions 2.5h after poisoning. AChE inhibition was associated with down regulation of synaptic AChE mRNA 24h after poisoning in cortex and striatum. Partial recovery of AChE activity was observed 24h after poisoning associated with increased catalytic efficiency (Km) of the enzyme. The recovery of AChE mRNA and protein levels to normal occurred in 7 days in cortex and cerebellum and over one month in striatum and hippocampus. ConclusionCholinergic neurotoxicity of acute severe monocrotophos poisoning is characterized by high acetylcholinesterase inhibition, downregulation of acetylcholinesterase mRNA and slow recovery of acetylcholinesterase activity in brain regions. De novo synthesized acetylcholinesterase is associated with increased catalytic efficiency that may contribute in restoring cholinergic function.

Brain regional acetylcholinesterase activity and muscarinic acetylcholine receptors in rats after repeated administration of cholinesterase inhibitors and its withdrawal

Activity of acetylcholinesterase (AChE) and specific binding of [(3)H]quinuclidinyl benzilate (QNB), [(3)H]pirenzepine (PZP) and [(3)H]AF-DX 384 to muscarinic acetylcholine receptor (mAChR) preparations in the striatum, hippocampus and cortex of rats were determined 1, 6 and 11 days after the last treatment with an organophosphate DDVP, a carbamate propoxur or a muscarinic agonist oxotremorine as a reference for 7 and 14 days. AChE activity was markedly decreased in the three regions 1 day after the treatment with DDVP for 7 and 14 days with a gradual recovery 6 to 11 days, and much less decreased 1, 6 and 11 days after the treatment with propoxur for 7 days but not for 14 days in the hippocampus and cortex. The binding of [(3)H]-QNB, PZP and AF-DX 384 in the three regions was generally decreased by the treatment with DDVP for 7 and 14 days. Such down-regulations were generally restored 6 or 11 days after the treatment for 7 but not for 14 days. The down-regulation or up-regulation as measured by [(3)H]-QNB, PZP and AF-DX 384 was observed 1, 6 or 11 days after treatment with propoxur for 7 days and/or 14 days. Repeated treatment with oxotremorine produced similar effects except AChE activity to DDVP. These results suggest that repeated inhibition of AChE activity may usually cause down-regulation of mAChRs with some exception in the hippocampus when a reversible antiChE propoxur is injected.

Increased expression of glial fibrillary acidic protein in cerebellum and hippocampus: differential effects on neonatal brain regional acetylcholinesterase following maternal exposure to combined chlorpyrifos and nicotine.

Cigarette smoking and environmental exposure to chlorpyrifos during pregnancy could lead to developmental toxicity in the offspring. In the present study, pregnant female Sprague-Dawley rats (300-350 g) were treated daily with nicotine (1 mg/kg, sc) or chlorpyrifos (0.1 mg/kg, dermal) or a combination of nicotine and chlorpyrifos from gestational days (GD) 4-20. Control animals were treated with saline and ethanol. Male offspring from the mothers treated with nicotine alone gained significantly less weight on postnatal day (PND) 30 as compared to control. On PND 7, there was a significant increase in brain acetylcholinesterase (AChE) activity in pups from nicotine- and chlorpyrifos-treated dams, whereas plasma butyrylcholinesterase (BChE) activity was significantly elevated in pups of mothers treated with either chlorpyrifos alone or pesticide combined with nicotine. On PND 30 there was a significant increase in AChE activity in brainstem and cerebellum in all treated male pups. In female pups on PND 30 there was a significant rise in AChE activity in brainstem of chlorpyrifos alone and in cerebellum of the combination nicotine and chlorpyrifos group. Histopathological evaluation demonstrated an increased neuronal cell death in the cerebellum granular cell layer of female offspring from nicotine or combined nicotine with chlorpyrifos group. A rise in glial fibrillary acidic protein (GFAP) immunostaining was observed in the CA1 subfield of hippocampus and cerebellum on PND 30 in female and male offspring of mothers treated with either nicotine or nicotine in combination with chlorpyrifos, but to a lesser extent in males. Data suggest that maternal exposure to nicotine and chlorpyrifos, alone or in combination, produces differential alterations in brain regional AChE activity and expression of GFAP in cerebellum and hippocampus in offspring on PND 30.

The effect of high and low dosages of paraoxon in beta-naphthoflavone-treated rats.

Aliesterases (carboxylesterases) are serine esterases that can serve a protective role for the target acetylcholinesterase (AChE) during organophosphorus insecticide intoxication because the former esterases are alternate phosphorylation sites. The levels of aliesterase activity in liver and plasma and AChE activity in brain regions were investigated after the intravenous administration of paraoxon (P = O) into female rats. The rats were pretreated intraperitoneally with beta-napthoflavone (BNF), which decreases hepatic aliesterase activity following a 3 day in vivo treatment, and/or tri-o-tolyl phosphate (TOTP) to inhibit aliesterases. The liver aliesterases were inhibited less by P = O in BNF-treated rats than in control rats, which suggests that either BNF exposure may have resulted in aliesterases that are less sensitive to P = O inhibition or BNF may have altered P = O's availability. The BNF treatment did not seem to alter the degree of inhibition of the brain AChE activity following the low dosage of paraoxon (0.04 mg/kg). However, the brain AChE activity in the P = O/TOTP/BNF-treated rats was lower than that in the P = O/TOTP-treated rats, suggesting that BNF also caused changes in systems affecting the disposition of P = O in addition to the changes in the hepatic aliesterases. At the high dosage of paraoxon (0.12 mg/kg), the AChE and aliesterase activities showed a pattern similar to that of the low dosage. This suggests that the aliesterases, as altered by BNF exposure, even when nearly completely inhibited, did not alter the response of the target enzyme, AChE, and, therefore, the magnitude of the toxic response.

Changes of acetylcholinesterase activity in three major brain areas and related changes in behaviour following acute treatment with diisopropyl fluorophosphate

In a series of experiments, the recovery of acetylcholinesterase activity in three brain regions following its depression by diisopropyl fluorophosphate was examined. Related changes in behaviour were also studied. The maximum depression in acetylcholinesterase activity in the anterior preoptic area occurred at 4hr, about the same time as the maximum depression of deep body temperature was recorded. A significant recovery of acetylcholinesterase activity was observed at 16hr, while temperature regulation returned to normal by 20 hr. Maximum depression of drinking behaviour and acetylcholinesterase activity in the lateral hypothalamus both occurred at approx. 1 hr following the acute diisopropyl fluorophosphate injections and both showed significant but not complete recovery by 24 hr. Single alternation performance had not completely recovered even at the final test session, i.e. 71 hr following the diisopropyi fluorophosphate injection, at which time acetylcholinesterase activity in the caudate nucleus had reached approximately 23% of normal. These findings generally support the hypothesis that recovery of certain behaviours may be dependent upon the renewed synthesis of acetylcholinesterase activity in brain regions which are important in mediating these behaviours.