The potential ameliorative effect of mesenchymal stem cells-derived exosomes on cerebellar histopathology and their modifying role on PI3k-mTOR signaling in rat model of autism spectrum disorder

Autism spectrum disorder (ASD) is a group of severe neurodevelopmental disorders. This study aimed to elucidate the potential ameliorating effect of postnatal administration of MSCs-derived Exo in a rat model of ASD. Male pups were divided into control (Cont), (VPA); pups of pregnant rats injected with VPA subcutaneously (S.C.) at embryonic day (ED) 13, and (VPA + Exo); pups were intravenously (I.V.) injected with MSCs-derived Exo either at postnatal day (P) 21 (adolescent VPA + Exo) or P70 (adult VPA + Exo). They were evaluated for physiological, histopathological and immunohistochemical changes of cerebellar structure, and genetic expression of PI3k and mTOR. The VPA adult group showed increased locomotor activity and impaired social activity, and anxiety. The cerebellar histological structure was disrupted in VPA groups. VPA + Exo groups showed preservation of the normal histological structure of the cerebellum. Immunohistochemical studies revealed enhanced expression of caspase-3, GFAP, Nestin, and VEGF in VPA groups beside modifying PI3K and mTOR genetic expression. MSCs-derived Exo ameliorated most of the rat cerebellar histopathological alterations and behavioral changes. Their mitigating effect could be established through their antiapoptotic, anti-inflammatory and anti-neurogenesis effect besides modifying PI3k-mTOR signaling.