Ameliorating effect of pioglitazone on prenatal valproic acid-induced behavioral and neurobiological abnormalities in autism spectrum disorder in rats

Autism spectrum disorder (ASD) is a neurodevelopment disorder that mainly arises due to abnormalities in different brain regions, resulting in behavioral deficits. Besides its diverse phenotypical features, ASD is associated with complex and varied etiology, presenting challenges in understanding its precise neuropathophysiology. Pioglitazone was reported to have a fundamental role in neuroprotection in various other neurological disorders. The present study aimed to investigate the therapeutic potential of pioglitazone in the prenatal valproic acid (VPA)-model of ASD in Wistar rats. Pregnant female Wistar rats received VPA on Embryonic day (E.D12.5) to induce autistic-like-behavioral and neurobiological alterations in their offspring. VPAexposed rats presented core behavioral symptoms of ASD such as deficits in social interaction, poor spatial and learning behavior, increased anxiety, locomotory and repetitive activity, and decreased exploratory activity. Apart from these, VPA exposure also stimulated neurochemical and histopathological neurodegeneration in various brain regions. We administered three different doses of pioglitazone i.e., 2.5, 5, and 10 mg/kg in rats to assess various parameters. Of all the doses, our study highlighted that 10 mg/kg pioglitazone efficiently attenuated the autistic symptoms along with other neurochemical alterations such as oxidative stress, neuroinflammation, and apoptosis. Moreover, pioglitazone significantly attenuated the neurodegeneration by restoring the neuronal loss in the hippocampus and cerebellum. Taken together, our study suggests that pioglitazone exhibits therapeutic potential in alleviating behavioral abnormalities induced by prenatal VPA exposure in rats. However, further research is needed to fully understand and establish pioglitazone's effectiveness in treating ASD.