老年性聋小鼠认知功能的下降及其机制

Mechanisms of cognitive function decline of the presbycusis mice model

目的观察C57BL/6J老年性聋小鼠认知功能的改变并探讨其机制。方法雄性C57BL/6J小鼠分为3月龄(青年)组和12月龄(中年)组。听性脑干反应(ABR)检测小鼠听功能,Morris水迷宫观察小鼠的空间学习和记忆能力,Western印迹检测小鼠海马和听皮层BDNF和pTrk B的蛋白表达。结果 12月龄小鼠8、16、24 k Hz和32 k Hz的听阈值与3月龄组比较明显上升(P<0.01),提示听功能严重损失。Morris水迷宫实验结果显示,从训练的第3天开始直到第5天,12月龄组小鼠潜伏期均显著高于3月龄组(P<0.01,P<0.05),12月龄组小鼠穿越平台次数显著低于3月龄组(P<0.01)。Western印迹结果发现,与3月龄小鼠比较,12月龄小鼠海马和听皮层BDNF蛋白表达无明显变化,p-Trk B蛋白表达降低。结论12月龄C57BL/6J小鼠即显示明显的认知功能下降,可能与其早发的老年性聋有一定关系,海马和听皮层Trk B蛋白的磷酸化可能是主要机制之一。

Objective To observe the cognitive function decline and the mechanisms of presbycusis mice model.Methods The male C57BL/6J mice aged 3 months（ young） and 12 months（ middle-aged） were used. Auditory brainstem response（ ABR） was used to test the hearing function. Morris water maze was used to examine the spatial learning and memory. Western blot was used to examine the BDNF and p-Trk B protein expression.Results ABR showed that the hearing threshold levels of 12 months old mice at 8,16,24 and 32 k Hz were higher than those of 3 months old mice（ P〈0.01）. The hidden platform test showed that the latency of 12 months old group was higher than that of 3 months old group from the third training day to the fifth training day（ P〈0.01,P〈0.05）. In probe test,the numbers of platform location crossing in 12 months old group increased significantly compared to that of 3 months old group（ P〈0.05）. Western blot showed that the expression levels of p-Trk B in 12 months old group decreased significantly compared to 3 months old group. The expression of BDNF had no difference between two groups.Conclusions The significant cognitive decline is found in C57BL/6J mice,which might be related to the early onset of presbycusis. The phosphorylation of Trk B in hippocampus and auditory cortex might be one of the mechanisms.