Novel role of peroxisome proliferator activated receptor-α in valproic acid rat model of autism: Mechanistic study of risperidone and metformin monotherapy versus combination
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder of heterogenous etiology exhibiting a challenge in understanding its exact neuro-pathophysiology. Recently, peroxisome proliferator activated receptor (PPAR)-α activation was found to play a fundamental role in neuroprotection and improving autistic-like-behaviors in experimental animal models of ASD through alleviating neuroinflammation, oxidative-stress, astrocyte reactivity, tauopathy in addition to its favorable role in metabolic regulation, thus attracting attention as a possible target in treatment of ASD. This study aimed to investigate the role of PPAR-α, astrocytic dysfunction and tauopathy in ASD and detect the possible neuroprotective effects of metformin (MET), through PPAR-α activation, and risperidone (RIS) either monotherapy or in combination in alleviating autistic-like-changes at behavioral and neurobiological levels in male Wistar rats. Pregnant female Wistar rats received valproic-acid (VPA) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic intra-peritoneal MET (100 mg/kg/day) and RIS (1 mg/kg/day) either monotherapy or in combination started from postnatal day (PND) 24 till PND61 (38 days). Prenatal VPA exposure simulated the autistic core behaviors associated with neurochemical and histopathological neurodevelopmental degenerative changes. Both MET and RIS either monotherapy or in combination were able to reverse these changes. The effect of MET…
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