Decreased acetylcholine release is correlated to memory impairment in the Tg2576 transgenic mouse model of Alzheimer's disease.
Acetylcholine (ACh) release is one of the key factors in memory mechanisms. To clarify whether beta-amyloid (Abeta) induces a disturbance of the cholinergic system leading to memory impairment, we examined memory impairment and measured hippocampal ACh release in Tg2576 (Tg) mice that over-express the Swedish mutant amyloid precursor protein (APPsw). Furthermore, we examined Abeta burden with aging. Tg mice aged 9-11 months, but not aged 4-6 months, showed memory impairment in the 8-arm radial maze behavior test. Spontaneous ACh release was not altered in Tg mice compared with age-matched control mice at 4-6 or 9-11 months of age. On the other hand, high-K(+)-evoked ACh release was decreased in Tg mice aged 9-11 months, but not in Tg mice aged 4-6 months. Hippocampal Abeta increased in an age-dependent manner, but evident amyloid plaques were not found in the hippocampus of Tg mice aged 11 months. These results suggest that memory impairment in Tg mice could be attributed to cholinergic synapse dysfunction that could not be caused predominantly by amyloid plaques. Measuring ACh release in this model might be a useful index for the screening of new drugs to treat the early-phase of Alzheimer's disease.
Watanabe
Takuya
T
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
Yamagata
Norito
N
Takasaki
Kotaro
K
Sano
Kazunori
K
Hayakawa
Kazuhide
K
Katsurabayashi
Shutaro
S
Egashira
Nobuaki
N
Mishima
Kenichi
K
Iwasaki
Katsunori
K
Fujiwara
Michihiro
M
D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000502:physiology; D011188:Potassium / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D000109:Acetylcholine; D011188:Potassium