BDNF在APP/PS1转基因小鼠皮层和海马内的表达及其对学习记忆能力的影响

目的:探究脑源性神经生长因子(BDNF)在野生型小鼠和APP/PS1双转基因小鼠大脑内的表达变化及其对学习记忆能力的影响。方法:选择野生型小鼠和APP/PS1双转基因小鼠作为研究对象,刚果红染色标记Aβ斑,TUNEL法检测细胞凋亡,采用免疫荧光和Western blot方法检测BDNF在野生型和APP/PS1双转基因小鼠皮层和海马内的表达,Morris水迷宫检测小鼠的空间学习记忆能力。结果:APP/PS1双转基因小鼠皮层和海马区都形成Aβ斑,且12月龄小鼠Aβ斑的数量多于6月龄(P<0.05)。12月龄APP/PS1双转基因小鼠皮层和海马区神经元凋亡的数量多于野生型小鼠(P<0.01)。野生型小鼠皮层和海马区BDNF的表达量高于APP/PS1双转基因小鼠(P<0.01)。水迷宫检测显示,APP/PS1双转基因小鼠的逃逸潜伏期长于野生型小鼠,而60 s内穿越平台所位象限的次数少于野生型小鼠,且游泳轨迹杂乱无章。结论:APP/PS1双转基因型小鼠皮层和海马区BDNF的表达量低于野生型小鼠,并伴随着神经元凋亡的增加,且空间学习记忆能力降低。这些结果提示APP/PS1双转基因小鼠学习记忆能力的降低可能与BDNF表达减少导致神经元凋亡增加有关,这也许是阿尔茨海默病的病理机制之一。

Effect of BDNF expression in cerebral cortex and hippocampus on ability of learning and memory in APP/PS1 transgenic mice

AIM:To investigate the expression changes of brain-derived neurotrophic factor(BDNF)in the cerebral cortex and hippocampus and their effects on the ability of learning and memory in the wild-type(WT)mice and APP/PS1 transgenic mice.METHODS:WT mice and APP/PS1 transgenic mice were selected as study subjects.Aβplaques,apoptosis rate and BDNF expression in the cerebral cortex and hippocampus of WT mice and APP/PS1 transgenic mice were detected by the methods of Congo red staining,TUNEL,immunofluorescence and Western blot.The abilities of learning and memory were determined by Morris water maze test.RESULTS:The Aβplaques appeared in the cerebral cortex and hippocampus of APP/PS1 transgenic mice,and the number of Aβplaques in 12-month-old mice was larger than that in 6-month-old mice(P<0.05).The number of apoptotic neurons in the cerebral cortex and hippocampus of 12-month-old APP/PS1 transgenic mice was larger than that of WT mice(P<0.01).The expression level of BDNF in the cerebral cortex and hippocampus of WT mice was higher than that of APP/PS1 transgenic mice(P<0.01).The Morris water maze test showed that the escape latency in APP/PS1 transgenic mice was longer than that in WT mice,and the times across the platform quadrant in 60 s was less than that in WT mice(P<0.01).The swim-tracking path of APP/PS1 transgenic mice was disordered and irregular.CONCLUSION:The expression of BDNF in the cerebral cortex and hippocampus of APP/PS1 transgenic mice was lower than that of WT mice,accompanied by increased neuronal apoptosis and decreased spatial learning and memory ability.The decrease in learning and memory ability may be related to decreased BDNF expression in the cerebral cortex and hippocampus of APP/PS1 transgenic mice,leading to increased neuronal apoptosis,which may be one of the pathological mechanisms of Alzheimer disease.