脑源性神经营养因子对苯丙氨酸诱导的Cdc42、Rac1和RhoA蛋白表达的影响  

Brain-derived neurotrophic factors inhibit phenylalanine-induced down-regulation of Cdc42, Rac1 , and RhoA protein expression in cultured cortical neurons

作　　者：张拥军[1] 袁小兵[2] 顾学范[1] 

机构地区：[1]上海交通大学医学院附属新华医院上海市儿科医学研究所,上海200092 [2]中国科学院神经科学研究所,上海200031

出　　处：《临床儿科杂志》2009年第11期1074-1078,共5页Journal of Clinical Pediatrics

基　　金：国家自然科学基金资助项目(No.30340082)

摘　　要：目的观察脑源性神经营养因子(BDNF)对苯丙氨酸诱导的神经元树突的生长及其Cdc42、Rac1和RhoA蛋白表达的影响。方法胎鼠大脑皮层神经元培养3 d后,加入0.9 mmol/L苯丙氨酸或同时加入100 ng/mlBDNF诱导,免疫组化标记神经元突起并计数,Western blotting检测Cdc42、Rac1和RhoA蛋白表达。结果神经元在苯丙氨酸诱导2 d后,苯丙氨酸减少了神经元树突数(P<0.01),而同时加入BDNF可改善苯丙氨酸诱导的神经元树突的减少(P<0.01)。并且BDNF抑制苯丙氨酸诱导的Cdc42、Rac1和RhoA蛋白表达下调。结论BDNF可能通过影响Cdc42、Rac1和RhoA表达改善苯丙氨酸所致的神经元损伤。BDNF对治疗苯丙酮尿症脑损伤可能具有潜在的应用价值。Objectives To explore whether phenylalanine affect Cdc42, Racl, and RhoA expression and disturb dendritic development. To determine the effects of brain-derived neurotrophic factor （BDNF） on this process. Methods Neurons were cultivate＇d up to 3 days and then treated with 0.9 mmol/L phenylalanine or 100 ng/ml BDNF. Dendritic number were determined by morphologic analysis. Cde42, Racl, and RhoA protein expression were examined by Western blotting analysis. Results The number of dendrites in cultured neurons reduced two days after being treated with phenylalanine, while BDNF could rescue this change （P 〈 0.01） , furthermore, BDNF was found to inhibit phenylalanineinduced down-regulation of Cdc42, Racl, and RhoA protein expression （P 〈 0.01）. Conclusions Our study indicated that the protective effect of BDNF against phenylalanine-induced neuronal injury is probably mediated by expression of Cde42, Racl, and RhoA. It suggested a potential neuroprotective action of BDNF in prevention and treatment of brain injury in the patients with phenylketonuria.

关 键 词：苯丙氨酸 脑源性神经营养因子 神经元树突 RHOGTPASES 

分 类 号：R725.8[医药卫生—儿科]