Loss of erbB signaling in oligodendrocytes alters myelin and dopaminergic function, a potential mechanism for neuropsychiatric disorders.
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.
Proceedings of the National Academy of Sciences of the United States of America
May 8, 2007
Agency: NINDS NIH HHS, Id: F31 NS048630
Agency: NINDS NIH HHS, Id: NS7473
Agency: NICHD NIH HHS, Id: P30-HD 18655
Agency: NIMH NIH HHS, Id: P50 MH066171
Agency: NIMH NIH HHS, Id: P50 MH66171
Agency: NIMH NIH HHS, Id: R01 MH60131
Agency: NINDS NIH HHS, Id: R01 NS035884
Agency: NINDS NIH HHS, Id: R01 NS35884
Agency: NIMH NIH HHS, Id: R43 MH070264
Cyclic Nucleotide Phosphodiesterases, Type 1
Nerve Tissue Proteins
Phosphoric Diester Hydrolases
Promoter Regions, Genetic
Receptor, Epidermal Growth Factor
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