应激及再应激后大鼠大脑皮质BDNF及细胞支架的改变

目的 研究慢性不可预见性温和应激（CUMS）,氟西汀治疗及再应激后大鼠大脑皮质脑源性神经营养因子（BDNF）及细胞支架微管系统的改变.方法 将32只大鼠随机分为4组：对照组（空白对照＋o.9％氯化钠溶液）,CUMS组（CUMS＋0.9％氯化钠溶液）,氟西汀组（CUMS＋氟西汀）,再应激组（CUMS＋氟西汀＋1周药物清洗期＋CUMS）.大鼠进行21 d CUMS后,氟西汀组给予氟西汀治疗21d,再应激组给予氟西汀治疗21d后进行1周药物清洗,再次给予CUMS.其余两组给予0.9％氯化钠溶液.实验结束后检测糖水偏好,并使用Western Blotting检测鼠大脑总皮质及额叶皮质Acet-Tub,Tyr-Tub,BDNF,总tau,磷酸化tau（Ser356及Thr231）的表达.结果 21 d慢性应激后,CUMS组糖水偏好（52.37±16.758）％与对照组（76.37±7.671）％比较差异有统计学意义（P＜0.01）;氟西汀组糖水偏好与对照组比较差异无统计学意义;CUMS再应激组糖水偏好（42.00±8.03）％与对照组及CUMS组比较差异均有统计学意义（P＜0.01）.与对照组比较,CUMS组大鼠额叶皮质Acet-Tub表达升高（174.53±13.7）,Tyr-Tub表达降低（64.00±9.24）,BDNF表达降低（67.94±9.81）,p-tau（Ser356）的表达（165.49±9.68）及p-tau（Thr231）的表达（210.83±23.12）升高,差异有统计学意义（P＜0.01）.经氟西汀治疗后,Acet-Tub表达降低,Tyr-Tub、BDNF的表达升高,p-tau（Ser356）及p-tau（Thr231）的表达降低,与对照组比较差异无统计学意义.再应激组Acet-Tub表达升高（250.46±15.72）,Tyr-Tub表达降低（33.54±10.23）,BDNF表达降低（34.77±6.24）,p-tau （Ser356）表达（237.42±10.24）及p-tau（Thr231）的表达（373.69±34.14）升高,与对照组及CUMS组比较差异均有统计学意义（P＜0.01）.4组之间总tau的表达比较差异无统计学意义.大鼠大脑总皮质各项指标差异无统计学意义.结论 抑郁动物模型大脑额叶皮质微管动态性减低,伴随BDNF表达减低

Changes of cytoskeleton and BDNF in the cortex of rats following chronic stress

Objective To investigate changes of cytoskeletal microtubular system and brain-derived neurotrophic factor （BDNF） in the cortex following chronic unpredictable mild stress （CUMS） and re-exposure to CUMS.Methods Totals 32 male Sprague-Dawley （SD） rats were divided into four groups,with 8 exposed to 21 consecutive days of CUMS and treated with vehicle,8 exposed to CUMS and treated with fluoxetine,8 exposed to CUMS and treated with fluoxetine and re-exposed to CUMS after washout,and 8 as healthy controls treated with vehicle.Sucrose preferences in these rats were analyzed.The expressions of cytoskeletal microtubular system and BDNF in the cortex were analyzed using western blot.Results Compared with the normal rats（76.37±7.671）％,sucrose preference （52.37± 16.758） ％ was reduced （P ＜0.01） in the depressed rats.These changes could be reversed after 21d fluoxetine treatment.Compared with the control and CUMS group,sucrose preference （42.00± 8.03）％ was reduced （P ＜ 0.01 for both） in the re-exposure to CUMS group.Compared with the normal rats,the Acet-Tub expression（174.53 ± 13.7） increased significantly,Tyr-Tub expression （64.00 ± 9.24） decreased significantly,the BDNF expression（67.94± 9.81） decreased significantly,the p-tau（Ser356） expression （165.49±9.68） and p-tau（Thr231） expression （210.83±23.12） showed a significant increase in the frontal cortex of rats submitted to CUMS（P＜0.01）.These changes could also be reversed after 21d fluoxetine treatment.Compared with the control and CUMS group,the Acet-Tub expression （250.46±15.72）,the p-tau（Ser356） expression （237.42± 10.24） and p-tau（Thr231） expression （373.69±34.14） showed a significant increase,Tyr-Tub expression （33.54± 10.23） and the BDNF expression （34.77± 6.24） showed a significant decrease of re-exposure to CUMS group.There are no significant changes in the total cortex of four groups.Conclusions These findings provide evidence that rats exposed to