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Dev Neurosci. 2002;24(5):437-45.

IGF-I and NT-3 signaling pathways in developing oligodendrocytes: differential regulation and activation of receptors and the downstream effector Akt.

Author information

1
Department of Neuroscience and Anatomy, Penn State College of Medicine, Hershey, Pa 17033, USA.

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.

PMID:
12666655
DOI:
10.1159/000069050
[Indexed for MEDLINE]

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