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Brain‐derived neurotrophic factor effects on oligodendrocyte progenitors of the basal forebrain are mediated through trkB and the MAP kinase pathway
Author(s) -
Van't Veer Ashlee,
Du Yangzhou,
Fischer Tanya Z.,
Boetig Deborah R.,
Wood Melissa R.,
Dreyfus Cheryl F.
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21841
Subject(s) - tropomyosin receptor kinase b , mapk/erk pathway , microbiology and biotechnology , brain derived neurotrophic factor , tropomyosin receptor kinase a , neurotrophic factors , neurotrophin , low affinity nerve growth factor receptor , biology , protein kinase b , kinase , chemistry , signal transduction , receptor , biochemistry
Abstract Previous work has indicated that BDNF increases the differentiation of basal forebrain (BF) oligodendrocytes (OLGs) in culture through the mediation of trkB and the MAPK pathway (Du et al. [ 2006a, b] Mol. Cell. Neurosci. 31:366–375; J. Neurosci. Res. 84:1692–1702). In the present work, effects of BDNF on BF OLG progenitor cells (OPCs) were examined. BDNF increased DNA synthesis of OPCs, as assessed by thymidine and bromodeoxyuridine incorporation. Effects of BDNF on DNA synthesis were mediated through the trkB receptor and not the p75 receptor, as shown by inhibitors that block neurotrophin binding to the receptors and by the phosphorylation of trkB. TrkB can activate the mitogen‐ activated protein kinase (MAPK), phosphatidylinositol‐3 kinase (PI3‐K), and phospholipase C‐γ (PLC‐γ) pathways. BDNF elicited the phosphorylation of MAPK and Akt, a kinase downstream of PI3K, but not PLC‐γ in OPCs. Through the use of specific inhibitors to the MAPK and PI3‐K pathways, it was found that the MAPK pathway was responsible for the effect of BDNF on DNA synthesis. These data indicate that BDNF affects OPC proliferation and development through the mediation of trkB and the MAPK pathway. © 2008 Wiley‐Liss, Inc.