Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 19, Pages 8131-8136Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0702157104
Keywords
dopamine; erbB receptor; neuregulin; schizophrenia; white matter
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Funding
- NICHD NIH HHS [P30 HD018655, P30-HD 18655] Funding Source: Medline
- NIMH NIH HHS [P50 MH66171, R01 MH60131, R01 MH060131, P50 MH066171, R43 MH070264] Funding Source: Medline
- NINDS NIH HHS [NS7473, F31 NS048630, T32 NS007473, R01 NS35884, R01 NS035884] Funding Source: Medline
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Several psychiatric disorders are associated with white matter defects, suggesting that oligodendrocyte (OL) abnormalities underlie some aspects of these diseases. Neuregulin 1 (NRG1) and its receptor, erbB4, are genetically linked with susceptibility to schizophrenia and bipolar disorder. In vitro studies suggest that NRG1-erbB signaling is important for OL development. To test whether erbB signaling contributes to psychiatric disorders by regulating the structure or function of OLs, we analyzed transgenic mice in which erbB signaling is blocked in OLs in vivo. Here we show that loss of erbB signaling leads to changes in OL number and morphology, reduced myelin thickness, and slower conduction velocity in CNS axons. Furthermore, these transgenic mice have increased levels of dopamine receptors and transporters and behavioral alterations consistent with neuropsychiatric disorders. These results indicate that defects in white matter can cause alterations in dopaminergic function and behavior relevant to neuropsychiatric disorders.
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