NRXN1 Depletion Induces Aberrant Locomotor Activity and Social Behavior Via Impairment of Neurite Outgrowth in Rat

Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental process. NDDs are associated with some high-risk gene mutations and share partially overlapping genetic abnormalities. Neurexins (NRXNs) have been found to be related to both autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). NRXN1 is recognized as an essential susceptibility gene for NDDs, but little is known on its role in neurodevelopmental behaviors. In this study, we found that down-regulation of NRXN1 induced aberrant locomotor activity and social behavior with impaired neurite outgrowth in primary neurons in NRXN1 knockdown rats. Moreover, Tandem Mass Tag (TMT) based proteomic analysis of rat brain samples showed that down-regulation of NRXN1 led to significant pathways alterations of extracellular matrix, cell membrane and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure. In summary, our results confirmed that suppression of NRXN1 might downregulate the proteins associated with morphology, impairing the neurogenesis, and eventually induced abnormal locomotor activity and social behavior behaviors in rat. These findings not only expand NRXN1 interactome, but also contributes to understand the importance of NRXN1 in the progression of neurodevelopmental behaviors.