Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations
Open accessAbstract
Chronic stress is a risk factor for the development of psychopathologies characterized by cognitive dysfunction and deregulated social behaviours. Emerging evidence suggests a role for cell adhesion molecules, including nectin-3, in the mechanisms that underlie the behavioural effects of stress. We tested the hypothesis that proteolytic processing of nectins by matrix metalloproteinases (MMPs), an enzyme family that degrades numerous substrates, including cell adhesion molecules, is involved in hippocampal effects induced by chronic restraint stress. A reduction in nectin-3 in the perisynaptic CA1, but not in the CA3, compartment is observed following chronic stress and is implicated in the effects of stress in social exploration, social recognition and a CA1-dependent cognitive task. Increased MMP-9-related gelatinase activity, involving N-methyl-D-aspartate receptor, is specifically found in the CA1 and involved in nectin-3 cleavage and chronic stress-induced social and cognitive alterations. Thus, MMP-9 proteolytic processing emerges as an important mediator of stress effects in brain function and behaviour.
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Stress is the leading cause of MMP-9 secretion in either patients or experimental animals.
“Stress is the leading cause of MMP-9 secretion in either patients or experimental animals [57, 58].”
From Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain (2022) · cites this paper as [57]
The Results section ('Increased gelatinolytic activity in the CA1 of stressed animals'; page unavailable) reports increased MMP-9 activation in the hippocampal CA1 of chronically stressed rats. The paper also notes elevated MMP-9 in macrophage cells from depressed patients, especially with high stress. Neither passage establishes that stress is the leading cause of MMP-9 secretion in patients or experimental animals; the reported measures concern elevation or activity, not secretion. (LLM, conf=0.87)
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- Authors
- van der Kooij, M. A., Fantin, M., Rejmak, E., Grosse, J., Zanoletti, O., Fournier, C., Ganguly, K., Kalita, K., Kaczmarek, L., & Sandi, C.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- Corresponding author
- Fantin, Martina
- Rejmak, Emilia
- Sandi, Carmen
- ORCID
- Venue
- Nature Communications
- Published
- 2014-09-18
- Volume
- 5
- Issue
- 1
- Pages
- 4995-4995
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4199199
- OpenAlex
- W1974054391
- Cited by
- 140
- References
- 64
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 12 · 2023: 11 · 2022: 15 · 2021: 4 · 2020: 20 · 2019: 10 · 2018: 15 · 2017: 11 · 2016: 9 · 2015: 12
- FWCI
- 5.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Science Foundation
- European Commission (31003AB-135710, 201600)
- École Polytechnique Fédérale de Lausanne (FP7-HEALTH-F2M-2007-201600, 31003AB-135710)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (152614, FP7-HEALTH-F2M-2007-201600, 135710)
- Fundacja na rzecz Nauki Polskiej
- FP7 Health
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- MMP-9, nectin-3, chronic restraint stress, hippocampal CA1, adhesion molecules, proteolytic processing, NMDA receptor, social exploration, social recognition, cognitive impairment, gelatinase activity
- MeSH terms
- Nectins, Aggression, Animals, Behavior, Animal, Cell Adhesion, Cognition, Male, Risk Factors, Social Behavior, Stress, Psychological, Cell Adhesion Molecules, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Matrix Metalloproteinase 9, Rats, CA1 Region, Hippocampal
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