脑源性神经营养因子/酪氨酸激酶受体B信号通路抑制剂K252a逆转丙戊酸引起的神经元过度生长  

BDNF/TrkB pathway inhibitor K252a reverses the neuronal overgrowth induced by valproic acid in vitro

作　　者：王中平[1] 熊小琴[1] 崔卫刚[2,3] 张应花[2,3] 李瑞锡[2] 

机构地区：[1]九江学院基础医学院免疫学教研室,九江332000 [2]复旦大学上海医学院人体解剖学与组织学胚胎学系,上海200032 [3]新乡医学院人体解剖学教研室,新乡453003

出　　处：《解剖学杂志》2013年第1期4-8,共5页Chinese Journal of Anatomy

基　　金：江西省教育厅科技项目（GJJ11620）;江西省自然科学基金（20i14BAB205063）;国家自然科学基金（81260211）

摘　　要：目的：探讨脑源性神经营养因子（BDNF）/酪氨酸激酶受体B（TrkB）信号通路抑制剂K252a是否对丙戊酸引起的神经元过度生长有逆转作用。方法：用丙戊酸及K252a分别或共处理大鼠大脑皮层原代培养神经元，定量RT-PCR及免疫印迹检测BDNF/TrkB通路蛋白BDNF及TrkB的表达变化，同时以免疫荧光技术观测神经元形态变化。结果：丙戊酸处理后，显著增加神经元BDNF- mRNA的表达，TrkB mRNA的表达则未见明显变化；丙戊酸处理也导致BDNF蛋白表达上调。而用K252a处理后，神经元BDNF及TrkB表达与对照组相比，无明显变化。形态学结果显示，丙戊酸处理后，神经元过度生长，表现为神经元突起数目及总长度显著增加；而K252a处理后，丙戊酸引起的神经元突起过度生长受到明显抑制。结论：BDNF/TrkB通路抑制剂K252a可逆转丙戊酸导致的神经元过度生长。该结果为丙戊酸及K252a应用于临床治疗某些神经发育与退行性疾病如自闭症及阿尔茨海默病等提供了实验依据。Objective： To investigate the reverse effect of K252a, an inhibitor of BDNF/TrkB pathway which plays an important role in the neuronal proliferation, differentiation and neurite growth, on the neuronal overgrowth induced by valproic acid （VPA）. Methods： The primary cultured neurons from the rat cortex were exposed to VPA, VPA plus K252a or the control. The expressions of BDNF and TrkB were tested by quantitative RT-PCR and Western blotting, and the morphological changes of the neurons were observed by immunofluorescence. Results： VPA exposure, in comparison with the control, increased the expression of both mRNA and protein of BDNF, but not of TrkB. However, K252a treatment did not affect the expression of BDNF and TrkB in the cultured neurons. The results also showed that VPA treatment promoted neuronal growth, manifesting as a significant increment of the number of the neurite branches and total neurite length. Furthermore, the promotion of neurite overgrowth induced by VPA could be partly reversed by K252 a. Conclusion： The BDNF/TrkB pathway inhibitor K252a could reverse the neuronal overgrowth induced by VPA in vitro, thus giving experimental data for the clinical application of VPA and K252a in the treatment of neurodevelopmental and neurodegenerative diseases such as autism and Alzheimer＇s disease etc.

关 键 词：丙戊酸 脑源性神经营养因子 酪氨酸激酶受体B 抑制剂K252a 神经元生长 

分 类 号：R322.811[医药卫生—人体解剖和组织胚胎学]