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キーワード:
Cell adhesion molecule; Neuroligin-2; Early life stress; Hippocampus; Social behavior; Aggression
要旨:
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.
