Anxiety- and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: Protective effects of voluntary physical exercise

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Abstract

Prenatal ethanol exposure can damage the developing nervous system, producing long-lasting impairments in both brain structure and function. In this study we analyzed how exposure to this teratogen during the period of brain development affects the intracellular redox state in the brain as well as the development of anxiety- and depressive-like phenotypes. Furthermore, we also tested whether aerobic exercise might have therapeutic potential for fetal alcohol spectrum disorders (FASD) by increasing neuronal antioxidant capacity and/or by alleviating ethanol-induced behavioral deficits. Sprague-Dawley rats were administered ethanol across all three-trimester equivalents (i.e., throughout gestation and during the first 10 days of postnatal life). Ethanol-exposed and control animals were assigned to either sedentary or running groups at postnatal day (PND) 48. Runners had free access to a running wheel for 12 days and at PND 60 anxiety- and depressive-like behaviors were assessed. Perinatal ethanol exposure resulted in the occurrence of depressive and anxiety-like behaviors in adult rats without affecting their locomotor activity. Voluntary wheel running reversed the depressive-like behaviors in ethanol-exposed males, but not in ethanol-exposed females. Levels of lipid peroxidation and protein oxidation were significantly increased in the hippocampus and cerebellum of ethanol-exposed rats, and there was a concomitant reduction in the levels of the endogenous antioxidant glutathione. Voluntary exercise was able to reverse the deficits in glutathione both in ethanol-exposed males and females. Thus, while voluntary physical exercise increased glutathione levels in both sexes, its effects at the behavioral level were sex dependent, with only ethanol-exposed male runners showing a decrease in depressive-like behaviors.

Highlights

▸ Perinatal ethanol exposure leads to anxiety and depression-like behaviors in rats. ▸ Exercise reverses depression-like behaviors in ethanol-exposed adult male rats. ▸ Perinatal ethanol exposure leads to an increase in oxidative stress in adult rats. ▸ Exercise restores glutathione levels in ethanol-exposed adult female and male rats. ▸ Exercise reduces oxidative stress by enhancing glutathione levels.

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