Chinese medical journal · 2001
Spatial learning deficits in amyloid precursor protein 770 transgenic mice.
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Li H, Shen X, Chen Y
Аннотация
OBJECTIVE: To determine whether learning 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 learning deficits in the Morris water maze and in spontaneous alternation 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 APP770 transgenic mice are accompanied by a decrease in cortical and hippocampal ChAT activities. This suggests that cholinergic deficits may be involved in the learning 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).
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 learning deficits in the Morris water maze and in spontaneous alternation 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 APP770 transgenic mice are accompanied by a decrease in cortical and hippocampal ChAT activities. This suggests that cholinergic deficits may be involved in the learning 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).