Decreased level of brain acetylcholine and memory disturbance in APPsw mice.
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.
Ikarashi
Yasushi
Y
Tsumura Research Institute Medical Evaluation Laboratory, 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Harigaya
Yasuo
Y
Tomidokoro
Yasushi
Y
Kanai
Mitsuyasu
M
Ikeda
Masaki
M
Matsubara
Etsuro
E
Kawarabayashi
Takeshi
T
Kuribara
Hisashi
H
Younkin
Steven G
SG
Maruyama
Yuji
Y
Shoji
Mikio
M
D000109:Acetylcholine / Q000378:metabolism*; D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011930:Reaction Time / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D000109:Acetylcholine