Mitogen-activated protein kinase pathway mediates effects of brain-derived neurotrophic factor on differentiation of basal forebrain oligodendrocytes
Mitogen-activated protein kinase pathway mediates effects of brain-derived neurotrophic factor on differentiation of basal forebrain oligodendrocytes
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DOI：
10.1002/jnr.21080
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发表时间：
2006-12-01
影响因子：
4.2
通讯作者：
Dreyfus, Cheryl F.
中科院分区：
文献类型：
--
作者：
Du, Yangzhou;Lercher, Lauren D.;Dreyfus, Cheryl F.
以往的研究表明，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（OLG）的分化性状的表达。具体地，BDNF上调髓磷脂碱性蛋白（MBP）、蛋白脂质蛋白（PLP）和髓磷脂相关糖蛋白的表达（MAG; Du等人[2006] Mol. Cell. Neurosci. 31：366-375）。然而，介导BDNF作用的信号级联尚未被定义。本研究采用生物化学和分子生物学方法来研究丝裂原活化蛋白激酶（MAPK）通路、磷脂酰肌醇-3激酶（PI 3 K）通路和磷脂酶C-γ（PLC-γ）通路的参与。我们的研究结果表明，在BF OLG中，BDNF激活MAPK通路和PLC-γ通路，但不激活PI 3 K-Akt信号级联。通过使用特异性抑制剂和突变的显性负性或组成型活性形式的MAPK激酶，我们证明了MAPK途径介导BDNF对BF OLG分化性状表达的影响。(c)2006 Wiley-Liss，Inc.
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. (c) 2006 Wiley-Liss, Inc.