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.
Roy
Kristine
K
Neurobiology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Murtie
Joshua C
JC
El-Khodor
Bassem F
BF
Edgar
Nicole
N
Sardi
S Pablo
SP
Hooks
Bryan M
BM
Benoit-Marand
Marianne
M
Chen
Chinfei
C
Moore
Holly
H
O'Donnell
Patricio
P
Brunner
Daniela
D
Corfas
Gabriel
G
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000209:etiology; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D004298:Dopamine / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology*; D001523:Mental Disorders / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009186:Myelin Sheath / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D009431:Neural Conduction; D020890:Neuregulin-1; D009836:Oligodendroglia / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D011401:Promoter Regions, Genetic; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000502:physiology*; D012919:Social Behavior
D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D000661:Amphetamine; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D010727:Phosphoric Diester Hydrolases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D004298:Dopamine