Hippocampal neuroligin-2 links early-life stress with impaired social recognition and increased aggression in adult mice
Open accessAbstract
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.
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In male mice, limited bedding and nesting material can increase aggression.
“In male mice, LBN can increase aggression (Kohl et al. 2015).”
From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Kohl et al. 2015
Sex-specific changes in social behavior have been demonstrated in the limited bedding and nesting material model.
“Sex-specific changes in social behavior have also been demonstrated (Kohl et al. 2015; Kooij et al. 2015; Breton et al. 2024).”
From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Kohl et al. 2015
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- Authors
- Kohl, C., Wang, X.-D., Grosse, J., Fournier, C., Harbich, D., Westerholz, S., Li, J.-T., Bacq, A., Sippel, C., Hausch, F., Sandi, C., & Schmidt, M. V.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Schmidt, Mathias V.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 55
- Pages
- 128-143
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2082977189
- Cited by
- 76
- References
- 6
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 3 · 2020: 9 · 2019: 6 · 2018: 10 · 2017: 7 · 2016: 7 · 2015: 6
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A-152614, 31003AB-135710)
- Oak Foundation
- École Polytechnique Fédérale de Lausanne
- European Commission (FP7-HEALTH-F2M-2007-201600)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- neuroligin-2, early life stress, hippocampus, social recognition, aggression, social cognition, neuronal cell adhesion molecule, viral overexpression, neuropsychiatric disorders, therapeutic target
- MeSH terms
- Aggression, Animals, Behavior, Animal, Hippocampus, Nerve Tissue Proteins, RNA, Messenger, Social Behavior, Social Perception, Stress, Psychological, Cell Adhesion Molecules, Neuronal, Mice, Gene Knockdown Techniques
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