Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 39, Pages 14052-14057Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0506713102
Keywords
fibroblast growth factor; hippocampus; schizophrenia; Sprouty4; electroconvulsive seizure
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Funding
- NIMH NIH HHS [R01-4R37MH59388, R37 MH059388] Funding Source: Medline
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The neuronal PAS domain protein 3 (NPAS3) gene encoding a brain-enriched transcription factor was recently found to be disrupted in a family suffering from schizophrenia. Mice harboring compound disruptions in the NPAS3 and related NPAS1 genes manifest behavioral and neuroanatomical abnormalities reminiscent of schizophrenia. Herein we demonstrate that Npas3(-/-) mice are deficient in expression of hippocampal FGF receptor subtype 1 mRNA, most notably in the dentate gyrus. In vivo BrdUrd-labeling shows that basal neural precursor cell proliferation in the dentate gyrus of Npas3(-/-) mice is reduced by 84% relative to wild-type littermates. We propose that a deficiency in adult neurogenesis may cause the behavioral and neuroanatomical abnormalities seen in Npas3(-/-) mice, and we speculate that impaired neurogenesis may be involved in the pathophysiology of schizophrenia.
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