Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations

Michael A. van der Kooij (), Martina Fantin (), Emilia Rejmak (), Jocelyn Grosse, Olivia Zanoletti, Celine Fournier, Krishnendu Ganguly, Katarzyna Kalita, Leszek Kaczmarek and Carmen Sandi ()
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Michael A. van der Kooij: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL
Martina Fantin: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL
Emilia Rejmak: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences
Jocelyn Grosse: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL
Olivia Zanoletti: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL
Celine Fournier: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL
Krishnendu Ganguly: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences
Katarzyna Kalita: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences
Leszek Kaczmarek: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences
Carmen Sandi: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms5995

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