title: Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations.
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.
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne 1015, Switzerland.
authors.forename: Michael A
authors.initials: MA
authors.lastname: van der Kooij
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne 1015, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Fantin
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street 02-093 Warsaw, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Rejmak
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne 1015, 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, Lausanne 1015, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Zanoletti
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne 1015, Switzerland.
authors.forename: Celine
authors.initials: C
authors.lastname: Fournier
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street 02-093 Warsaw, Poland.
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Ganguly
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street 02-093 Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kalita
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street 02-093 Warsaw, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne 1015, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
mesh_terms: D000374:Aggression; D000818:Animals; D001522:Behavior, Animal; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003071:Cognition; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D000075983:Nectins; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012307:Risk Factors; D012919:Social Behavior; D013315:Stress, Psychological
chemical_list: D015815:Cell Adhesion Molecules; D000075983:Nectins; D016194:Receptors, N-Methyl-D-Aspartate; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat