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HERO ID
1600030
Reference Type
Journal Article
Title
Chronic exposure of mutant DISC1 mice to lead produces sex-dependent abnormalities consistent with schizophrenia and related mental disorders: A gene-environment interaction study
Author(s)
Abazyan, B; Dziedzic, J; Hua, K; Abazyan, S; Yang, C; Mori, S; Pletnikov, MV; Guilarte, TR
Year
2014
Is Peer Reviewed?
1
Journal
Schizophrenia Bulletin
ISSN:
0586-7614
EISSN:
1745-1701
Volume
40
Issue
3
Page Numbers
575-584
Language
English
PMID
23716713
DOI
10.1093/schbul/sbt071
Web of Science Id
WOS:000334750800016
Abstract
The glutamatergic hypothesis of schizophrenia suggests that hypoactivity of the N-methyl-d-aspartate receptor (NMDAR) is an important factor in the pathophysiology of schizophrenia and related mental disorders. The environmental neurotoxicant, lead (Pb(2+)), is a potent and selective antagonist of the NMDAR. Recent human studies have suggested an association between prenatal Pb(2+) exposure and the increased likelihood of schizophrenia later in life, possibly via interacting with genetic risk factors. In order to test this hypothesis, we examined the neurobehavioral consequences of interaction between Pb(2+) exposure and mutant disrupted in schizophrenia 1 (mDISC1), a risk factor for major psychiatric disorders. Mutant DISC1 and control mice born by the same dams were raised and maintained on a regular diet or a diet containing moderate levels of Pb(2+). Chronic, lifelong exposure of mDISC1 mice to Pb(2+) was not associated with gross developmental abnormalities but produced sex-dependent hyperactivity, exaggerated responses to the NMDAR antagonist, MK-801, mildly impaired prepulse inhibition of the acoustic startle, and enlarged lateral ventricles. Together, these findings support the hypothesis that environmental toxins could contribute to the pathogenesis of mental disease in susceptible individuals.
Keywords
DISC1; MRI; NMDA receptor; Pb2+exposure; gene-environment interaction; schizophrenia
Tags
NAAQS
•
ISA-Lead (2013 Final Project Page)
•
ISA - Lead (2024 Final Project Page)
Included in Peer Input Draft
Appendix 3 (Nervous System Effects)
Included in External Review Draft
Appendix 3 (Nervous System Effects)
Included in Final Draft
Appendix 3 (Nervous System Effects)
Title-Abstract Screening (SWIFT-AS) - Included
Title-Abstract Screening (SWIFT-AS) - Included
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