Mitogen-activated protein kinase pathway mediates effects of brain-derived neurotrophic factor on differentiation of basal forebrain oligodendrocytes.
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-gamma (PLC-gamma) pathway. Our results indicate that, in BF OLGs, BDNF activates the MAPK pathway and the PLC-gamma 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.
Du
Yangzhou
Y
Department of Neuroscience and Cell Biology, UMDNJ/Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Lercher
Lauren D
LD
Zhou
Renping
R
Dreyfus
Cheryl F
CF
D000256:Adenoviridae / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects*; D011247:Pregnancy; D016548:Prosencephalon / Q000166:cytology*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D020929:Mitogen-Activated Protein Kinase Kinases