The Involvement of Hippocampal Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder: Role of the Neuropeptide Oxytocin

Abstract

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder generally signified by a disruption in social interaction and communication combined with frequent repetitive patterns of behaviors or interests. Although the cellular and molecular changes in autistic brains are unclear, the neuropathological abnormalities of ASD have been identified in several brain areas, including the hippocampus. The participation of neuroinflammation and oxidative stress to ASD induction and perpetuation has also been identified. It has been reported that the levels of reactive oxygen species (ROS) and several neuroinflammatory cytokines are abnormally increased in hippocampal brain area in individuals with ASD. Neuroinflammation and oxidative stress are also known as major factors for the induction of programmed cell death (apoptosis). Apoptosis is a fundamental process known to regulate cellular growth. Disordered apoptosis and cellular death involve a number of signal transduction cascade steps resulting from the activation of pro-apoptotic proteins and inhibition of antiapoptotic ones. According to many postmortem and animal studies, abnormalities of several apoptotic signaling pathways have been linked to the induction of ASD, one being the p53 signaling pathway. Therefore, agents that can reduce neuroinflammation and oxidative stress like the neuropeptide oxytocin may effectively manage ASD. It has been shown that oxytocin can reduce neuroinflammation and oxidative stress and improve neuronal cell growth in some neural cell lines. Therefore, this review focuses on the role of oxytocin in the management of ASD through its protective effects against neuroinflammation and oxidative stress in the hippocampal brain area.