IGF-I and NT-3 Signaling Pathways in Developing Oligodendrocytes: Differential Regulation and Activation of Receptors and the Downstream Effector Akt

Abstract

A previous study from our laboratory demonstrated differences in the ability of insulin-like growth factor-I (IGF-I) and neurotrophin-3 (NT-3) to promote survival of pro-oligodendroblasts (pro-OLs) against glutamate-mediated apoptosis. In the current study, we tested whether submaximal concentrations of NT-3 would maintain receptor tyrosine kinase TrkC activation and Akt phosphorylation and thus promote long-term survival of the pro-OL against glutamate. Our results demonstrate that NT-3 at any concentration sufficient to activate the TrkC receptor results in a transient phosphorylation of the receptor and of Akt due, in part, to downregulation of the Trk receptor. In contrast, even submaximal IGF-I concentrations maintain long-term Akt activation and prevent glutamate-mediated apoptosis in pro-OLs. In addition, we also present data showing that IGF-I and NT-3 differentially activate their receptors and Akt depending on the maturational stage of the oligodendrocyte.