期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 19, 页码 7076-7081出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0802615105
关键词
bipolar disorder; gene; mouse model; working memory; adult neurogenesis
资金
- NIGMS NIH HHS [T32GM008224, T32 GM008224] Funding Source: Medline
- NIMH NIH HHS [R01 MH067068, MH67068, MH77235, MH080234, R01 MH077235, R01 MH080234] Funding Source: Medline
- NINDS NIH HHS [P01 NS048120] Funding Source: Medline
DISC1 is a strong candidate susceptibility gene for schizophrenia, bipolar disorder, and depression. Using a mouse strain carrying an endogenous Disc1 orthologue engineered to model the putative effects of the disease-associated chromosomal translocation we demonstrate that impaired Disc1 function results in region-specific morphological alterations, including alterations in the organization of newly born and mature neurons of the dentate gyrus. Field recordings at CA3/CA1 synapses revealed a deficit in short-term plasticity. Using a battery of cognitive tests we found a selective impairment in working memory (WM), which may relate to deficits in WM and executive function observed in individuals with schizophrenia. Our results implicate malfunction of neural circuits within the hippocampus and medial prefrontal cortex and selective deficits in WM as contributing to the genetic risk conferred by this gene.
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