Psychosocial Stress Induces Schizophrenia-Like Behavior in Mice With Reduced MMP-9 Activity

• Main Authors: Behnam Vafadari, Shiladitya Mitra, Marzena Stefaniuk, Leszek Kaczmarek
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-08-01
• Series: Frontiers in Behavioral Neuroscience
• Subjects: gene × environment (G×E) interaction; schizophrenia; negative symptoms; clozapine; antipsychotic; MMP-9
• Online Access: https://www.frontiersin.org/article/10.3389/fnbeh.2019.00195/full

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.