Du Yangzhou, Lercher Lauren D, Zhou Renping, Dreyfus Cheryl F
Department of Neuroscience and Cell Biology, UMDNJ/Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
J Neurosci Res. 2006 Dec;84(8):1692-702. doi: 10.1002/jnr.21080.
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.
先前的研究表明，脑源性神经营养因子（BDNF）通过trkB受体的介导，调节基底前脑（BF）少突胶质细胞（OLGs）中分化特征的表达。具体而言，BDNF上调髓鞘碱性蛋白（MBP）、蛋白脂蛋白（PLP）和髓鞘相关糖蛋白（MAG）的表达（Du等人，[2006]《分子与细胞神经科学》31:366 - 375）。然而，介导BDNF作用的信号级联反应尚未明确。当前的研究采用生化和分子生物学方法来检测丝裂原活化蛋白激酶（MAPK）途径、磷脂酰肌醇-3激酶（PI3K）途径和磷脂酶C-γ（PLC-γ）途径的参与情况。我们的结果表明，在BF OLGs中，BDNF激活MAPK途径和PLC-γ途径，但不激活PI3K-Akt信号级联反应。通过使用特异性抑制剂以及MAPK激酶的突变显性负性或组成型活性形式，我们证明MAPK途径介导了BDNF对BF OLGs中分化特征表达的影响。
