Decreased level of brain acetylcholine and memory disturbance in APPsw mice
Decreased level of brain acetylcholine and memory disturbance in APPsw mice
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DOI：
10.1016/s0197-4580(03)00122-2
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发表时间：
2004-04-01
影响因子：
4.2
通讯作者：
Shoji, M
中科院分区：
文献类型：
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作者：
Ikarashi, Y;Harigaya, Y;Shoji, M
为了阐明淀粉样β蛋白（Abeta）淀粉样变性是否诱导胆碱能系统紊乱，导致长期记忆障碍，我们连续检查记忆障碍使用被动回避任务，并测量APPsw转基因小鼠脑中的Abeta负荷和乙酰胆碱浓度。被动回避任务的重复保持试验表明，APPsw小鼠的长时记忆障碍从近似7.75月龄开始出现，并进行性发展。在10个月大的小鼠大脑中发现乙酰胆碱水平显着下降。8月龄时大脑皮质和海马出现少量老年斑，随年龄增长，老年斑的大小和数量逐渐增多。脑A β 40/42（43）的浓度从8月龄开始逐渐增加，此后呈指数增加。长期记忆障碍的进展与A β 40/42（43）负荷密切相关。这些结果表明，Abeta蓄积诱导长期记忆障碍和胆碱能系统的紊乱，被动回避任务和测量乙酰胆碱是评价该小鼠模型以及Abeta蓄积的有用方法。(C)2003年由Elsevier Inc.出版
To clarify whether amyloid beta protein (Abeta) amyloidosis induces a disturbance of cholinergic system leading to long-term memory deficits, we continuously examined memory disturbance using the passive-avoidance task, and measured Abeta burden and concentrations of acetylcholine in the brain of APPsw transgenic mice. Repetitive retention trials of the passive-avoidance task showed that the long-term memory impairment in APPsw mice appeared from similar to7.75 months old and progressively advanced. Significant decreases in acetylcholine levels were found in the brains of 10-month-old mice. A few senile plaques appeared in the cerebral cortex and the hippocampus at 8 months old, and increased in size and number with aging. The concentrations of brain Abeta40/42(43) gradually increased from 8 months old and exponentially increased thereafter. Advance of long-term memory disturbance was closely correlated with Abeta40/42(43) burden. These findings suggested that Abeta accumulation induced long-term memory impairment and disturbance of the cholinergic system, and that the passive-avoidance task and measuring acetylcholine were useful methods for evaluating this mouse model as well as Abeta accumulation. (C) 2003 Published by Elsevier Inc.