title: Brain-derived neurotrophic factor effects on oligodendrocyte progenitors of the basal forebrain are mediated through trkB and the MAP kinase pathway.
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-gamma (PLC-gamma) pathways. BDNF elicited the phosphorylation of MAPK and Akt, a kinase downstream of PI3K, but not PLC-gamma 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.
authors.affiliation: Department of Neuroscience and Cell Biology, UMDNJ/Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Ashlee
authors.initials: A
authors.lastname: Van't Veer
authors.forename: Yangzhou
authors.initials: Y
authors.lastname: Du
authors.forename: Tanya Z
authors.initials: TZ
authors.lastname: Fischer
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Boetig
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Wood
authors.forename: Cheryl F
authors.initials: CF
authors.lastname: Dreyfus