Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination.
We examined the role of IGF signaling in the remyelination process by disrupting the gene encoding the type 1 IGF receptor (IGF1R) specifically in the mouse brain by Cre-mediated recombination and then exposing these mutants and normal siblings to cuprizone. This neurotoxicant induces a demyelinating lesion in the corpus callosum that is reversible on termination of the insult. Acute demyelination and oligodendrocyte depletion were the same in mutants and controls, but the mutants did not remyelinate adequately. We observed that oligodendrocyte progenitors did not accumulate, proliferate, or survive within the mutant mice, compared with wild type, indicating that signaling through the IGF1R plays a critical role in remyelination via effects on oligodendrocyte progenitors.
Mason
Jeffrey L
JL
Department of Pathology and The Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA. jm1306@columbia.edu
Xuan
Shouhong
S
Dragatsis
Ioannis
I
Efstratiadis
Argiris
A
Goldman
James E
JE
D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000502:physiology; D003337:Corpus Callosum / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D003471:Cuprizone / Q000633:toxicity; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology; D009154:Mutation; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013002:Somatomedins / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D013002:Somatomedins; D014409:Tumor Necrosis Factor-alpha; D003471:Cuprizone; D017526:Receptor, IGF Type 1