Prefrontal Nectin3 Reduction Mediates Adolescent Stress-Induced Deficits of Social Memory, Spatial Working Memory, and Dendritic Structure in Mice

Hong-Li Wang 1,2 • Ji-Tao Li 1 • Han Wang 1 • Ya-Xin Sun1 • Rui Liu1 • Xiao-Dong Wang 3 • Yun-Ai Su1 • Tian-Mei Si 1


1 National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital/Institute of Mental Health) and the Key Laboratory of Mental Health, Ministry of Health (Peking University Sixth Hospital), Beijing 100191, China

2 The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100088, China

3 Department of Neurobiology, Key Laboratory of Medical Neurobiology of The Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310003, China

Abstract

Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain (especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses, but the underlying molecular mechanisms remain unclear. Here, we investigated how synaptic cell adhesion molecules (e.g., nectin3) are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex (mPFC). Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77. One week later, the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory, simplified dendritic structure, and reduced spine density in the mPFC. Membrane localization of nectin3 was also altered, and was significantly correlated with behavioral performance. Furthermore, knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology. These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.

Keywords

Adolescence; Chronic stress; Cell adhesion molecule; Prefrontal cortex; Social memory

[SpringerLink]

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