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Mitogen-activated protein kinase pathway mediates effects of brain-derived neurotrophic factor on differentiation of basal forebrain oligodendrocytes

✍ Scribed by Yangzhou Du; Lauren D. Lercher; Renping Zhou; Cheryl F. Dreyfus

Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
504 KB
Volume
84
Category
Article
ISSN
0360-4012

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✦ Synopsis

Abstract

Previous studies indicate that brain‐derived neurotrophic factor (BDNF), through the mediation of the trkB receptor, modulates the expression of differentiated traits in basal forebrain (BF) oligodendrocytes (OLGs). Specifically, BDNF up‐regulates the expression of myelin basic protein (MBP), proteolipid protein (PLP), and myelin associated glycoprotein (MAG; Du et al. [2006] Mol. Cell. Neurosci. 31:366–375). However, the signaling cascades mediating the effects of BDNF have not been defined. The current study employs biochemical and molecular biological approaches to examine the involvements of the mitogen‐activated protein kinase (MAPK) pathway, the phosphatidylinositol‐3 kinase (PI3K) pathway, and the phospholipase C‐γ (PLC‐γ) pathway. Our results indicate that, in BF OLGs, BDNF activates the MAPK pathway and the PLC‐γ pathway but not the PI3K‐Akt signaling cascade. By using specific inhibitors and mutated dominant negative or constitutively active forms of MAPK kinase, we demonstrate that the MAPK pathway is mediating the effects of BDNF on expression of differentiated traits in BF OLGs. © 2006 Wiley‐Liss, Inc.

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