Hippocampal neuroligin-2 links early-life stress with impaired social recognition and increased aggression in adult mice

被引：54

作者：

Kohl, Christine ^{[1
,2
]}

Wang, Xiao-Dong ^{[2
,3
]}

Grosse, Jocelyn ^{[1
]}

Fournier, Celine ^{[1
]}

Harbich, Daniela ^{[2
]}

Westerholz, Soeren ^{[2
]}

Li, Ji-Tao ^{[4
]}

Bacq, Alexandre ^{[1
]}

Sippel, Claudia ^{[2
]}

Hausch, Felix ^{[2
]}

Sandi, Carmen ^{[1
]}

Schmidt, Mathias V. ^{[2
]}

机构：

[1] Ecole Polytech Fed Lausanne, Sch Life Sci, Brain Mind Inst, Lab Behav Genet, CH-1015 Lausanne, Switzerland

[2] Max Planck Inst Psychiat, Dept Stress Neurobiol & Neurogenet, D-80804 Munich, Germany

[3] Zhejiang Univ, Sch Med, Zhejiang Prov Key Lab Neurobiol, Dept Neurobiol,Key Lab Med Neurobiol,Minist Hlth, Hangzhou 310058, Zhejiang, Peoples R China

[4] Peking Univ, Inst Mental Hlth, Beijing 100191, Peoples R China

来源：

PSYCHONEUROENDOCRINOLOGY | 2015年 / 55卷

基金：

瑞士国家科学基金会;

关键词：

Cell adhesion molecule; Neuroligin-2; Early life stress; Hippocampus; Social behavior; Aggression; CELL-ADHESION; INHIBITORY SYNAPSES; CHILDHOOD; BEHAVIOR; NEUROENDOCRINE; NEUREXINS; AUTISM; GENE; SCHIZOPHRENIA; CONSEQUENCES;

D O I：

10.1016/j.psyneuen.2015.02.016

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Early-life stress is a key risk factor for the development of neuropsychiatric disorders later in life. Neuronal cell adhesion molecules have been strongly implicated in the pathophysiology of psychiatric disorders and in modulating social behaviors associated with these diseases. Neuroligin-2 is a synaptic cell adhesion molecule, located at the postsynaptic membrane of inhibitory GABAergic synapses, and is involved in synaptic stabilization and maturation. Alterations in neuroligin-2 expression have previously been associated with changes in social behavior linked to psychiatric disorders, including schizophrenia and autism. In this study, we show that early-life stress, induced by limited nesting and bedding material, leads to impaired social recognition and increased aggression in adult mice, accompanied by increased expression levels of hippocampal neuroligin-2. Viral overexpression of hippocampal neuroligin-2 in adulthood mimics early-life stress-induced alterations in social behavior and social cognition. Moreover, viral knockdown of neuroligin-2 in the adult hippocampus attenuates the early-life stress-induced behavioral changes. Our results highlight the importance of neuroligin-2 in mediating early-life stress effects on social behavior and social cognition and its promising role as a novel therapeutic target for neuropsychiatric disorders. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：128 / 143

页数：16

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