脑老化导致学习记忆损害及其与髓鞘结构改变的关系

Injury of learning and memory induced by brain aging and the relationship with the changes of myelin structure

目的探讨脑老化时认知功能改变、髓鞘结构和成分变化及其之间关系。方法使用穿梭箱、电镜和免疫组织化学技术,观察了老年大鼠学习、记忆维持功能、髓鞘和轴突的超微结构改变,以及髓鞘碱性蛋白表达变化。结果在训练第1天至第6天,老年大鼠主动逃避反应率(AAR)、总逃避反应(GAR)率较青年组显著减慢(P<0.01),逃避潜伏时(LER)较青年组延长(P<0.01),训练第6天青年组GAR达到(89.0±6.6)%,老年只有(40.5±6.8)%,青年组LER为(3.16±0.47)s,老年组为(6.10±0.71)s。在记忆功能维持上,训练后第5天和第10天,老年组大鼠AAR、GAR很快降低,LER明显升高,较青年组差异有显著性(P<0.01)。老年大鼠髓鞘异常为轴突周围间隙扩大,髓鞘致密层分离,部分板层结构破坏,髓鞘内形成大泡,轴突直径增加,轴突内含有吞噬小泡、致密颗粒和巨大线粒体,少突胶质细胞电子密度增加。老年大鼠髓鞘碱性蛋白(MBP)表达下降。结论老年大鼠学习及记忆维持能力降低,老化可以导致轴突及髓鞘的结构变化,MBP表达降低,髓鞘结构和成分改变可能参与老化时学习和记忆损害。

Objective To investigate the changes of cognitive function, myelin structures and components, the relationship among them. Methods The learning and the maintenance of memory, the changes of the ultrastructure in myelin and axon, and the expression of myelin basic protein（MBP） were observed by the shuttle box apparatus, electron microscope and immunohistochemistry in aged rat. Results During 1-6 day of behavior training, active avoidance response （AAR） and general avoidance response （GAR） in aged rat group slower significantly than that in young rat group. The latency of escaping response （LER） prolongs significantly than that in young group. GARis （40.5±6.8）% and （89.0±6.6）%, LERis （6.10±0.71）s and （3.16±0.47）s re spectively in the aged group and young group at 6 day during training. AAR and GAR decreased fast, LER increased sharply in aged group at 5 day and 10 day after training, there are significant changes comparing with that in young group. The common abnormalities of the myelin sheaths in aged rat were a distended periaxonal space between the axon and myelin sheaths, splitting of the dense line of myelin sheaths, the disorder of lamellae structure to forming blister in the sheath, breakdown of myelin. There were the enlarged axons contained vacuoles and dense granules, giant mitochondria（Mt）. The electron density in cytoplasm of oligodendrocyte increased. The expression of myelin basic protein decreased with age. Conclusion The learning and memory were reduced with age. Aging can result in the structure changes of axon and myelin, and decline of MBP expression. The alteration of the structure and components in myelin may contribute to the injury of learning and memory during aging.