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Psychosocial stress induces schizophrenia-like-behavior in mice with reduced MMP-9 activity.
Front. Behav. Neurosci. 13:195 (2019)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Antipsychotic ; Clozapine ; Gene × Environment (g×e) Interaction ; Mmp-9 ; Negative Symptoms ; Schizophrenia; Nmda Receptor Hypofunction; Animal-models; Risk-factor; Matrix-metalloproteinase-9; Environment; Genes; Prevalence; Plasticity; Clozapine; Health
ISSN (print) / ISBN
1662-5153
e-ISSN
1662-5153
Zeitschrift
Frontiers in Behavioral Neuroscience
Quellenangaben
Band: 13,
Artikelnummer: 195
Verlag
Frontiers
Verlagsort
Lausanne
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Environmental Medicine (IEM)