Abstract
Abstract
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.
Graphical abstract
Funder
National Natural Science Foundation of China
the Natural Science Foundation of Jiangsu Province
the Subproject of Key Research and Development Program of China
the Jiangsu Provincial Medical Innovation Team
Six Talent Peaks Project in Jiangsu Province
the Key Project Supported by Medical Science and Technology Development Foundation Nanjing Department of Health
Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul
Publisher
Springer Science and Business Media LLC
Subject
Cognitive Neuroscience,Neurology (clinical),Pathology and Forensic Medicine,Pediatrics, Perinatology and Child Health
Cited by
1 articles.
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