Decreased level of brain acetylcholine and memory disturbance in APPsw mice.
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| Abstract |
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 approximately 7.75 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.
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| Authors | Yasushi Ikarashi, Yasuo Harigaya, Yasushi Tomidokoro, Mitsuyasu Kanai, Masaki Ikeda, Etsuro Matsubara, Takeshi Kawarabayashi, Hisashi Kuribara, Steven G Younkin, Yuji Maruyama, Mikio Shoji |
| Journal | Neurobiology of aging (Neurobiol Aging) Vol. 25 Issue 4 Pg. 483-90 (Apr 2004) ISSN: 0197-4580 [Print] United States |
| PMID | 15013569 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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