Calhoun Michael E, Mao Ying, Roberts Jeffrey A, Rapp Peter R
Kastor Neurobiology of Aging Laboratories, Fishberg Research Center for Neurobiology, Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
J Comp Neurol. 2004 Jul 19;475(2):238-46. doi: 10.1002/cne.20181.
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.
基底前脑胆碱能系统的改变在脑衰老和阿尔茨海默病中已得到广泛研究，但衰退的程度以及与认知障碍的关系仍存在争议。恒河猴（猕猴）为研究与年龄相关的记忆衰退提供了一个极具说服力的模型，因为其损伤模式与人类观察到的情况极为相似。在此，我们使用针对囊泡乙酰胆碱转运体的抗体和一种新的体视学技术，来估计行为特征明确的年轻和老年恒河猴海马亚区胆碱能纤维的总长度。分析显示，胆碱能纤维长度与年龄相关的下降幅度为22%，在所研究的海马亚区（齿状回颗粒细胞层和分子层、CA2/3-海马回以及CA1）以及海马的前后范围中均相似。然而，这种效应与延迟非匹配样本任务的表现无关，该任务是一种对猴子海马系统功能障碍和认知衰老敏感的识别记忆测试。这些发现表明，胆碱能输入的下降无法解释正常衰老对灵长类海马区域支持的记忆的影响。
