Evaluation of prenatal administration of valproic acid on the cerebellum of albino rat offspring

Abstract

Introduction: Autism is a severe neurodevelopmental disorder of poorly understood etiology; which may be genetic, epigenetic or environmental. Valproic acid (VPA), the most widely used antiepileptic drug, has been reported to increase the risk of autism among the offspring of human mothers who are medicated with it during early pregnancy. Aim: The current work aimed to study the biochemical and histological changes in the cerebellum of the offspring of prenatally VPA treated rats. Materials and Methods: Twelve pregnant female albino rats were divided into two groups; control and VPA treated (50 mg/kg/day orally). The cerebellar sections of male offspring rats were subjected to biochemical tests (brain tissue Malondialdehyde (MDA), Superoxide dismutase (SOD), Tumor necrosis factor-alpha (TNF-α) and glutamate), histological examination, immunohistochemical analyses for the expression of glial fibrillary acidic protein (GFAP) and Bcl-2 associated X protein (Bax), and electro microscopical studies. Results: VPA caused significant elevation in the brain levels of oxidative stress marker MDA, proinflammatory cytokine TNF-α and excitatory neurotransmitter glutamate, with significant reduction in the level of brain antioxidant marker SOD, compared to the control group.