Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome
Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome
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DOI：
10.1016/j.nlm.2007.05.007
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发表时间：
2008-02-01
影响因子：
2.7
通讯作者：
Gold, Paul E.
中科院分区：
文献类型：
--
作者：
Chang, Qing;Gold, Paul E.
在4个月、10个月和16个月大的对照组和Ts65Dn小鼠(唐氏综合症的部分三体模型)中，评估了空间工作记忆和胆碱酯酶抑制剂增强记忆的能力，这可能也与阿尔茨海默病有显著关系。此外，在4个月、10个月和22-25个月龄时，使用活体微透析从海马区收集样本，测量记忆测试期间ACh的释放。当测试四臂自发交替任务时，Ts65Dn小鼠在4个月和10个月时都表现出记忆得分受损。在16个月时，Ts65Dn小鼠的控制能力已经下降，而且不同基因类型的得分差异不显著。毒扁豆碱(50微克/公斤)完全逆转了4个月大组Ts65Dn小鼠的记忆缺陷，但对老年小鼠没有。Ts65Dn和对照组小鼠在所有被测试的年龄显示出相似的ACh释放基线水平；在任何一种基因型中，这些水平都没有随着年龄的增长而显著下降。在交替试验中，只有Ts65Dn和对照组小鼠的ACh释放量显著增加。然而，在交替测试中，对照组小鼠ACh释放的增加明显大于这个年龄段的Ts65Dn小鼠。对照组在与测试相关的ACh释放的增加中显示出与年龄相关的显著下降。由于年轻的Ts65Dn小鼠在测试过程中仅略有增加，这些小鼠ACh释放对测试的反应性随年龄的下降并不显著。总体而言，这些结果表明，海马区ACh释放对行为测试的反应性减弱可能导致Ts65Dn小鼠的记忆障碍。(C)2007 Elsevier Inc.保留所有权利。
Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer's disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22-25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 mu g/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice. (C) 2007 Elsevier Inc. All rights reserved.