摘要目的观察APP770转基因小鼠的空间学习记忆能力是否出现变化以及该变化是否伴随着胆碱乙酰基转移酶(ChAT)活性的改变。方法选用鼠龄分别为3个月、6个月和9个月的转基因和非转基因雌性小鼠，每组为8只。行为学研究的手段有Y迷宫、Morris型水迷宫和十字迷宫。行为学实验后，对小鼠脑组织不同部位(皮层、海马、纹状体和下丘脑)中胆碱乙酰基转移酶的活性进行测定。结果与同龄对照小鼠比较，9个月的转基因小鼠空间学习记忆能力出现了明显的减退，并且其皮层和海马组织里ChAT的活性也明显减少，但纹状体和下丘脑里ChAT的活性则没有明显变化。鼠龄为3个月和6个月的转基因小鼠与对照鼠比较，其空间学习记忆能力则没有变化，并且ChAT的活性也基本没有改变。结论 9个月的转基因小鼠空间学习记忆能力出现了明显减退伴随着皮层和海马组织里ChAT活性的明显减少，提示转基因小鼠胆碱能系统的变化可能与学习记忆能力的改变有关。

abstractsTo determine whether leaming deficits could be seen in transgenic mice expressing human amyloid precursor protein 770 (APP770).Methods Female heterozygous transgenic and nontransgenic mice aged 3, 6 and 9 months at the start of testing were used, with eight mice in each age group. All mice were subjected to various behavioral tasks including the Y-maze task and the Morris water maze. After behavioral testing, the mice were sacrificed,and their brain tissues were used for measuring the choline acetyltransferase (CHAT) activity.Results Nine-month-old transgenic mice exhibited spatial learming deficits in the Morris water maze and in spontaneous altemation in the Y-maze, compared with those of the age-matched non-transgenic mice. The behavioral changes accompanied a reduction of ChAT activity in the cortical and hippocampal regions of transgenic mice. On the other hand, these behavioral deficits were not observed in transgenic mice either at 3 or at 6 months of age, in which ChAT activity remained unchanged.Conclusions The present results show that the learning impairment observed in 9-month-old APP770transgenic mice are accompanied by a decrease in cortical and hippocampal ChAT activities. This suggests that cholinergic deficits may be involved in the leaming impairment observed in these APP770 mice. This model will be a useful tool in advancing our understanding of the relationship between the cholinergic system and the cognitive deficits observed in Alzheimer's disease (AD).State Key Laboratory of Reproductive Biology (Li H), Department of Molecular Biology and Biotechnology (Shen XZ), Institute of Zoology,The Chinese Academy of Sciences, Beijing 100080, China