Van't Veer Ashlee, Du Yangzhou, Fischer Tanya Z, Boetig Deborah R, Wood Melissa R, Dreyfus Cheryl F
Department of Neuroscience and Cell Biology, UMDNJ/Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
J Neurosci Res. 2009 Jan;87(1):69-78. doi: 10.1002/jnr.21841.
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.
先前的研究表明，脑源性神经营养因子（BDNF）通过trkB和丝裂原活化蛋白激酶（MAPK）信号通路的介导作用，增加培养的基底前脑（BF）少突胶质细胞（OLGs）的分化（Du等人，[2006a，b]《分子与细胞神经科学》31:366 - 375；《神经科学研究杂志》84:1692 - 1702）。在本研究中，检测了BDNF对BF少突胶质前体细胞（OPCs）的影响。通过胸苷和溴脱氧尿苷掺入法评估，BDNF增加了OPCs的DNA合成。如阻断神经营养因子与受体结合的抑制剂以及trkB的磷酸化所示，BDNF对DNA合成的影响是通过trkB受体而非p75受体介导的。TrkB可激活丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶（PI3-K）和磷脂酶C-γ（PLC-γ）信号通路。BDNF可诱导OPCs中MAPK和Akt（PI3K下游的一种激酶）的磷酸化，但不诱导PLC-γ的磷酸化。通过使用针对MAPK和PI3-K信号通路的特异性抑制剂，发现MAPK信号通路介导了BDNF对DNA合成的作用。这些数据表明，BDNF通过trkB和MAPK信号通路的介导作用影响OPCs的增殖和发育。
