title: Hippocampal neuroligin-2 links early-life stress with impaired social recognition and increased aggression in adult mice.
abstract: 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.
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, 1015 Lausanne, Switzerland; Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, 80804 Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Kohl
authors.affiliation: Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, 80804 Munich, Germany; Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, 310058 Hangzhou, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Grosse
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Fournier
authors.affiliation: Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, 80804 Munich, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Harbich
authors.affiliation: Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, 80804 Munich, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Westerholz
authors.affiliation: Institute of Mental Health, Peking University, No. 51 Hua Yuan Bei Road, 100191 Beijing, China.
authors.forename: Ji-Tao
authors.initials: JT
authors.lastname: Li
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bacq
authors.affiliation: Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, 80804 Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sippel
authors.affiliation: Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, 80804 Munich, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Hausch
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
authors.affiliation: Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, 80804 Munich, Germany. Electronic address: mschmidt@mpipsykl.mpg.de.
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
mesh_terms: D000374:Aggression / Q000502:physiology* / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012919:Social Behavior; D012938:Social Perception; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism / Q000523:psychology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C098003:neuroligin 2
keywords: Aggression; Cell adhesion molecule; Early life stress; Hippocampus; Neuroligin-2; Social behavior