Tom R. Guilarte, Ph.D.
Columbia University Mailman School of Public Health
NIEHS Grants R01ES006189, ViCTER supplement to R01ES006189
An NIEHS grantee reports that mice engineered with a genetic risk factor for schizophrenia and exposed to lead during early life showed schizophrenic-like behaviors and structural changes in their brains. The findings suggest a gene-environment interaction is at work and supports the hypothesis that environmental contaminants could contribute to the development of mental disorders in susceptible people.
Recent studies in people suggest a possible association between prenatal exposure to lead and an increased likelihood of developing schizophrenia later. To find out more, the researchers looked at the consequences of lead exposure on mice with a mutant form of the human Disrupted-in-Schizophrenia-1 (mDISC1) gene, which is a risk factor for major psychiatric disorders. The mDISC1 mice that received lifelong exposure to lead showed schizophrenic-like behaviors and brain changes. These mice also had stronger responses to an n-methyl-d-aspartate receptor (NMDAR) antagonist. Some scientists hypothesize that NMDAR is an important factor in the pathophysiology of schizophrenia, and lead is a strong and selective antagonist of the NMDAR.
Citation: Abazyan B, Dziedzic J, Hua K, Abazyan S, Yang C, Mori S, Pletnikov MV, Guilarte TR. 2013. Chronic Exposure of Mutant DISC1 Mice to Lead Produces Sex-Dependent Abnormalities Consistent With Schizophrenia and Related Mental Disorders: A Gene-Environment Interaction Study. Schizophr Bull. 2013 May 28. [Online 28 May 2013].