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

摘要

Objective 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 cultivated 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. Cdc42, 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 Cdc42, Racl, and RhoA. It suggested a potential neuroprotective action of BDNF in prevention and treatment of brain injury in the patients with phenylketonuria.%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 mmo/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Cde42、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、Racl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.