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

Nat Commun. 2014 Sep 18;5:4995. doi: 10.1038/ncomms5995.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression
  • Animals
  • Behavior, Animal
  • CA1 Region, Hippocampal / metabolism*
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism*
  • Cognition
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Nectins
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Risk Factors
  • Social Behavior
  • Stress, Psychological


  • Cell Adhesion Molecules
  • Nectins
  • Receptors, N-Methyl-D-Aspartate
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat