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Front. Behav. Neurosci. | doi: 10.3389/fnbeh.2019.00195

Psychosocial Stress Induces Schizophrenia-like-behavior in Mice with Reduced MMP-9 Activity

  • 1Technical University of Munich, Germany
  • 2Nencki Institute of Experimental Biology (PAS), Poland

Understanding gene¬-environment interactions in the pathogenesis of schizophrenia remains a major research challenge. Matrix metalloproteinase-9 (MMP-9) has been previously implicated in the pathophysiology of schizophrenia. In the present study, adolescent Mmp-9 heterozygous mice, with a genetically lower level of MMP-9, were subjected to resident-intruder psychosocial stress for 3 weeks and then examined in behavioral tests that evaluated cognitive deficits and positive- and negative-like symptoms of schizophrenia. Cognitive and positive symptoms in unstressed Mmp-9 heterozygous mice were unaffected by stress exposure, whereas negative symptoms were manifested only after stress exposure. Interestingly, negative symptoms were ameliorated by treatment with the antipsychotic drug clozapine. We describe a novel gene  environment interaction mouse model of schizophrenia. Lower MMP-9 levels in the brain might be a risk factor for schizophrenia that in combination with environmental factors (e.g., psychosocial stress) may evoke schizophrenia-like symptoms that are sensitive to antipsychotic treatment.

Keywords: gene x environment interaction, GxE, schizophrenia negative symptoms, Clozapine, Anti-psychotic, MMP-9

Received: 14 May 2019; Accepted: 13 Aug 2019.

Copyright: © 2019 Vafadari, Mitra, Stefaniuk and Kaczmarek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Leszek Kaczmarek, Nencki Institute of Experimental Biology (PAS), Warszawa, 02-093, Masovian, Poland, l.kaczmarek@nencki.gov.pl