Oxidative stress and brain-derived neurotrophic factor interplay involve in the cognitive impairment induced by perinatal ethanol exposure in offspring

Background and Aim: Ethanol consumption during pregnancy reduces hippocampal brain-derived neurotrophic factor (BDNF), induces oxidative stress and causes deficit in the learning and memory of offspring. We used vitamin E as potent antioxidant to determine whether oxidative stress plays a role as a mediator of BDNF effect on learning and memory deficits induced by ethanol. Methods Pregnant Wistar rats received ethanol (۴ g/kg) and vitamin E (doses of ۱۰۰, ۲۰۰, and ۴۰۰ mg/kg) on gestation day (GD) ۰ until weaning (۲۸ days). The performance of spatial learning and memory of rats were measured using the Morris water maze (MWM) on postnatal days (PND) ۲۹. Superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities, reduced and oxidized glutathione (GSH and GSSG) levels, GSH/GSSG ratio, protein carbonyl content, and malondialdehyde (MDA) levels as a marker of lipid peroxidation were measured in the hippocampus of offspring. The hippocampal BDNF and cyclic AMP-response element-binding (CREB) protein expression levels were measured by real-time quantitative PCR. Also, BDNF, proBDNF, CREB and Phosphorylated CREB (P-CREB) protein levels were measured by western blot. Results: The aim of this study is to determine whether oxidative stress mediates BDNF effect on learning and memory deficits induced by ethanol. Conclusion: Ethanol exposure group showed reduced time spent in the target quadrant, higher escape location latency and average proximity in the probe test. Vitamin E (۴۰۰ mg/kg) significantly increased time spent in target quadrant, decreased escape location latency and average proximity in the probe test. Ethanol exposure significantly reduced GPx, SOD, and catalase activities, GSH, GSH/GSH ratio and increased MDA levels and carbonyl content in the hippocampus. Also, expression and protein levels of BDNF and CREB significantly reduced in the hippocampus by ethanol exposure. In addition, vitamin E administration could reduce oxidative stress, normalized BDNF and CREB levels, preserved activation of CREB and improved cognitive dysfunction induced by ethanol exposure. We conclude that oxidative stress can interact with the BDNF system for modulating cognitive function in the perinatal ethanol exposure rat.

کلیدواژه ها:

Ethanol ، Vitamin E ، Spatial memory ، Oxidative stress ، Brain-derived neurotrophic factor ، Rat offspring