NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat.

Autor: Wu, Di, Zhu, Jiansheng, You, Lianghui, Wang, Jingyu, Zhang, Sufen, Liu, Zhonghui, Xu, Qu, Yuan, Xiaojie, Yang, Lei, Wang, Wei, Tong, Meiling, Hong, Qin, Chi, Xia
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Zdroj: Journal of Neurodevelopmental Disorders; 2/3/2023, Vol. 15 Issue 1, p1-14, 14p
Abstrakt: Background: Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities. Methods: Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs. Results: NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure. Conclusions: Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health. Highlights: NRXN1 depletion induced anxiety-like behaviors and abnormal social phenotypes in rats. Knockdown of NRXN1 impaired neurite outgrowth in primary neurons. Downregulation of NRXN1 might downregulate the proteins associated with cell morphology and membrane structure [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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