Neuroprotective effects of the 17beta-estradiol against ethanol-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: biochemical, histological and behavioral changes.

摘要

During particular periods of central nervous system (CNS) development, exposure to ethanol can decrease regional brain growth and can result in selective loss of neurons. Unfortunately, there are few effective means of attenuating damage in the immature brain. In this study, the possible antioxidant and neuroprotective properties of 17beta-estradiol against ethanol-induced neurotoxicity was investigated. 17beta-estradiol (600 mug/kg) was injected subcutaneously in postnatal day (PD) 4 and 5, 30 min prior to intraperitoneal injection of ethanol (6g/kg) in rat pups. Ninety minutes after injection of ethanol, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (Gpx) in vermis of cerebellum were assayed. Thiobarbituric acid reactive substance (TBARS) levels were also measured as a marker of lipid peroxidation. Behavioral studies, including rotarod and locomotor activity tests were performed in PD 21-23 and histological study was performed after completion of behavioral measurements in postnatal day 23. The results of the present work demonstrated that ethanol could induce lipid peroxidation, increase TBARS levels and decrease glutathione peroxidase levels in pup cerebellum. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rat pups. However, treatment with 17beta-estradiol significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidants. Histological analysis also indicated that ethanol could decrease vermis Purkinje cell count and 17beta-estradiol prevented this toxic effect. These results suggest that ethanol may induce lipid peroxidation in the rat pups cerebellum while treatment with 17beta-estradiol improves motor deficits by protecting the cerebellum against ethanol toxicity.