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J Neurochem. 2005 Nov;95(4):1091-107.

Intracellular events mediating insulin-like growth factor I-induced oligodendrocyte development: modulation by cyclic AMP.

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Servicio de Endocrinología, Hospital Ramón y Cajal, Madrid, Spain.


Insulin-like growth factor I (IGF-I) is a potent inducer of oligodendrocyte development and myelination. Although IGF-I intracellular signaling has been well described in several cell types, intracellular mechanisms for IGF-I-induced oligodendrocyte development have not been defined. By using specific inhibitors of intracellular signaling pathways, we report here that the MAPK and phosphatidylinositol 3-kinase signaling pathways are required for the full effect of IGF-I on oligodendrocyte development in primary mixed rat cerebrocortical cell cultures. The MAPK activation, but not the phosphatidylinositol 3-kinase activation, leads to phosphorylation of the cAMP response element-binding protein, which is necessary for IGF-I to induce oligodendrocyte development. cAMP, although it does not show any effect on oligodendrocyte development, has an inhibitory effect on IGF-I-induced oligodendrocyte development that is mediated by the cAMP-dependent protein kinase. Furthermore, cAMP also has an inhibitory effect on IGF-I-dependent MAPK activation. This is a cAMP-dependent protein kinase-independent effect and probably contributes to the cAMP action on IGF-I-induced oligodendrocyte development.

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