Construction of an animal model of autism based on interaction between cerebellar histological, immunohistochemical, and biochemical changes in adult male albino rat

Autism spectrum disorder (ASD) represents a heterogeneous group of neurodevelopmental conditions characterized by impaired social interaction, language deficit, and stereotype behavior. This study was designed to construct an autistic animal model on the basis of histological and immunohistochemical changes in the rat cerebellum. Twelve pregnant female rats were divided into a control group and a valproic acid (VPA) treated group (injected intraperitoneally on embryonic day 12 with 600 mg/kg body weight of VPA). Neurobehavioral tests were conducted on the offspring of both groups. The cerebellum was studied by light and electron microscopy as well as GFAP and caspase-3 immunohistochemical staining. The VPA-treated group showed signs of neuronal degeneration, such as congested blood vessels, vacuolations, irregularly shrunken with dark small heterochromatic nuclei and numerous apoptotic blebs in the Purkinje and granule cells with vacuolated cerebellar glomeruli. The myelinated nerve fibers showed rarefaction and loss of their neurofilaments. GFAP and caspase-3 immune expression were significantly altered in the VPA-treated group. The VPA rat model can serve as an excellent model of autism at the structural level, which may be used as a validated model in preclinical studies to evaluate novel drugs.