Brain-derived neurotrophic factor effects on oligodendrocyte progenitors of the basal forebrain are mediated through TrkB and the MAP kinase pathway

Ashlee Van't Veer, Yangzhou Du, Tanya Z. Fischer, Deborah R. Boetig, Melissa R. Wood, Cheryl F. Dreyfus

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

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 (P13-K), and phospholipase: C-γ (PLC-γ) pathways. BDNF elicited the phosphorylation of MAPK and Akt, a kinase downstream of P13K, but not PLC-γ in OPCs. Through the use of specific inhibitors to the MAPK and P13-K pathways, it was found that the MAPK pathway was responsible for the effect of BDNF on DNA synthesis. These data indicate that BDNF-effects OPC proliferation and development through the mediation of trkB and the MAPK pathway.

Original languageEnglish (US)
Pages (from-to)69-78
Number of pages10
JournalJournal of Neuroscience Research
Volume87
Issue number1
DOIs
StatePublished - 2009

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Keywords

  • MAPK
  • Proliferation
  • TrkB
  • p75 NTR

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