PDF(Pubmed)
Abstract：
The cerebellum is involved in higher order cognitive function and is susceptible to age-related atrophy. However, limited evidence has directly examined the cerebellum\'s role in cognitive aging. To interrogate potential substrates of the relationship between cerebellar structure and memory in aging, here we target the Purkinje cells (PCs). The sole output neurons of the cerebellum, PC loss and/or degeneration underlie a variety of behavioral abnormalities. Using a rat model of normal cognitive aging, we immunostained sections through the cerebellum for the PC-specific protein, calbindin-D28k. Although morphometric quantification revealed no significant difference in total PC number as a function of age or cognitive status, regional cell number was a more robust correlate of memory performance in the young cerebellum than in aged animals. Parallel biochemical analysis of PC-specific protein levels in whole cerebellum additionally revealed that calbindin-D28k and Purkinje cell protein-2 (pcp-2) levels were lower selectively in aged rats with spatial memory impairment compared to both young animals and aged rats with intact memory. These results suggest that cognitive aging is associated with cerebellum vulnerability, potentially reflecting disruption of the cerebellum-medial temporal lobe network.
摘要：
小脑参与更高阶的认知功能，并且容易发生与年龄相关的萎缩。然而,有限的证据直接研究了小脑在认知衰老中的作用。为了询问小脑结构与记忆之间的关系的潜在底物，在这里，我们的目标是浦肯野细胞（PC）。小脑的唯一输出神经元，PC丧失和/或变性是各种行为异常的基础。使用正常认知老化的大鼠模型，我们对小脑的部分进行了PC特异性蛋白的免疫染色，Calbindin-D28k.尽管形态定量显示PC总数与年龄或认知状态的关系没有显着差异，与老年动物相比，年轻小脑的区域细胞数量与记忆表现的相关性更强。对整个小脑中PC特异性蛋白水平的平行生化分析还显示，与年轻动物和老年大鼠相比，具有空间记忆障碍的老年大鼠的钙结合蛋白-D28k和浦肯野细胞蛋白2（pcp-2）水平选择性较低记忆完整。这些结果表明，认知老化与小脑脆弱性有关，可能反映小脑-内侧颞叶网络的破坏。
