Wang Zhi-ling, Mao Meng, Zhou Hui, Li Sheng-fu, Yu Dan
Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Nov;38(6):934-7.
To investigate the changes of TrkB and Ras-MAPK in brain-derived neurotrophic factor (BDNF) protecting the embryonic rat cerebral cortical neurons against hypoxia-induced neurotoxicity.
The immunofluorescence technique, laser scanning confocal microscope and half-quantitative analysis were done to explore the changes of the intracellular levels of tyrosine kinase B (TrkB), phosphorylated TrkB and the mitogen-activated protein kinase (MAPK) in rat embryonic cortical neurons cultured in different time groups of hypoxia with or without BDNF pretreatment.
The fluorescent intensity of TrkB and phosphorylated TrkB in the cytoplasm and the fluorescent intensity of MAPK in both cytoplasm and cell nucleus of the neurons were significantly increased in the presence of BDNF (P < 0.05), the fluorescent intensity of neurons pretreated with BDNF 24 h before the hypoxia culture was stronger than those with BDNF just before the hypoxia culture (P < 0.05).
The Ras-MAPK approach may be the major signal transferring way of BDNF in protecting the cortical neurons from hypoxia-induced neurotoxicity. The approach of signal transferring begins with tyrosine phosphorylation of TrkB receptors.
探讨脑源性神经营养因子（BDNF）保护胚胎大鼠大脑皮质神经元免受缺氧诱导神经毒性作用过程中酪氨酸激酶B（TrkB）和Ras-丝裂原活化蛋白激酶（MAPK）信号通路的变化。
采用免疫荧光技术、激光扫描共聚焦显微镜及半定量分析方法，观察在不同缺氧时间组培养的大鼠胚胎皮质神经元中，有无BDNF预处理时细胞内TrkB、磷酸化TrkB及丝裂原活化蛋白激酶（MAPK）水平的变化。
BDNF存在时，神经元胞质中TrkB及磷酸化TrkB荧光强度以及胞质和细胞核中MAPK荧光强度均显著增加（P<0.05），缺氧培养前24 h用BDNF预处理的神经元荧光强度强于缺氧培养前即刻用BDNF预处理的神经元（P<0.05）。
Ras-MAPK信号通路可能是BDNF保护皮质神经元免受缺氧诱导神经毒性作用的主要信号转导途径，该信号转导途径始于TrkB受体的酪氨酸磷酸化。
