Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys
Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys
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DOI：
10.1002/cne.20181
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发表时间：
2004-07-19
影响因子：
2.5
通讯作者：
Rapp, PR
中科院分区：
文献类型：
--
作者：
Calhoun, ME;Mao, Y;Rapp, PR
基底前脑胆碱能系统的改变在脑老化和阿尔茨海默病中得到了广泛的研究，但下降的幅度及其与认知障碍的关系仍存在争议。恒河猴(Macaca Mulatta)提供了一个令人信服的模型来研究与年龄相关的记忆衰退，因为这种损害模式与在人类中观察到的非常相似。在这里，我们使用了针对囊泡乙酰胆碱转运体的抗体和一种新的体视学技术来估计行为特征为年轻和老年恒河猴的海马区胆碱能纤维的总长度。分析显示，与年龄相关的胆碱能纤维长度减少了22%，这在所研究的海马亚区(齿状回颗粒细胞和分子层、CA2/3门和CA1)以及海马嘴-尾端范围内都是相似的。然而，这种影响与延迟不匹配样本任务的表现无关，延迟不匹配样本任务是一项测试，测试对海马体系统功能障碍和认知老化敏感的识别记忆。这些发现表明，胆碱能输入的下降不能解释正常衰老对灵长类海马区支持的记忆的影响。(C)2004年Wiley-Liss公司
Alterations in the basal forebrain cholinergic system have been widely studied in brain aging and Alzheimer's disease, but the magnitude of decline and relationship to cognitive impairment are still a matter of debate. The rhesus monkey (Macaca mulatta) provides a compelling model to study age-related memory decline, as the pattern of impairment closely parallels that observed in humans. Here, we used antibodies against the vesicular acetylcholine transporter and a new stereological technique to estimate total cholinergic fiber length in hippocampal subregions of behaviorally characterized young and aged rhesus monkeys. The analysis revealed an age-related decline in the length of cholinergic fibers of 22%, which was similar across the hippocampal subregions studied (dentate gyrus granule cell and molecular layers, CA2/3-hilus, and CA1), and across the rostral-caudal extent of the hippocampus. This effect, however, was unrelated to performance on the delayed nonmatching-to-sample task, a test of recognition memory sensitive to hippocampal system dysfunction and cognitive aging in monkeys. These findings indicate that a decline in cholinergic input fails to account for the influence of normal aging on memory supported by the primate hippocampal region. (C) 2004 Wiley-Liss, Inc.