Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism.

ABSTRACT

Autism is a complex neurodevelopmental disorder characterized by impaired social communication and social interactions, and repetitive behaviors. The etiology of autism remains unknown and its molecular basis is not yet well understood. Pregnant Sprague-Dawley (SD) rats were administered 600 mg/kg of valproic acid (VPA) by intraperitoneal injection on day 12.5 of gestation. Both 11- to 13-week-old male and female rat models of VPA-induced autism showed impaired sociability and impaired preference for social novelty as compared to the corresponding control SD rats. Significantly reduced mRNA expressions of social behavior-related genes, such as those encoding the serotonin receptor, brain-derived neurotrophic factor and neuroligin3, and significantly increased expression levels of proinflammatory cytokines, such as interleukin-1 ß and tumor necrosis factor-α, were noted in the hippocampi of both male and female rats exposed to VPA in utero. The hippocampal expression level of gamma amino butyric acid (GABA) enzyme glutamic acid decarboxylase (GAD) 67 protein was reduced in both male and female VPA-exposed rats as compared to the corresponding control animals. Our results indicate that developmental exposure to VPA affects the social behavior in rats by modulating the expression levels of social behavior-related genes and inflammatory mediators accompanied with changes in GABA enzyme in the hippocampus.