Spatial memory impairment without apoptosis induced by the combination of beta-amyloid oligomers and cerebral ischemia is related to decreased acetylcholine release in rats.
The purpose of the present study was to examine the effect of beta-amyloid (Abeta) oligomers, not the fibrils that make up Abeta plaques, on spatial memory and the cholinergic system in rats. Recently, several researchers have suggested that small assemblies of Abeta, Abeta oligomers, caused memory loss during the early stages of Alzheimer's disease without showing cell death. In the present study, the combination of Abeta oligomers and cerebral ischemia, but not cerebral ischemia alone, significantly impaired spatial memory without apoptosis in the CA1 region of the hippocampus. Donepezil, an acetylcholinesterase inhibitor, ameliorated this memory impairment. Therefore we examined acetylcholine (ACh) release from the dorsal hippocampus. A microdialysis study showed that spontaneous release of ACh was not significantly decreased by the combination of Abeta oligomers and cerebral ischemia; however, high K(+)-evoked ACh release was decreased. These results suggest that a combination of Abeta oligomers and cerebral ischemia induces memory impairment by cholinergic synapse dysfunction without apoptosis. This model may be useful for developing new drugs for the treatment of early-phase Alzheimer's disease.
Watanabe
Takuya
T
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Jonan-ku, Fukuoka, Japan.
Iwasaki
Katsunori
K
Ishikane
Shin
S
Naitou
Tetsuya
T
Yoshimitsu
Yoshitaka
Y
Yamagata
Norito
N
Ozdemir
Mehmeto Bülent
MB
Takasaki
Kotaro
K
Egashira
Nobuaki
N
Mishima
Kenichi
K
Fujiwara
Michihiro
M
D000109:Acetylcholine / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D000077265:Donepezil; D015536:Down-Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007189:Indans / Q000494:pharmacology; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D017551:Microdialysis; D010446:Peptide Fragments / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D007189:Indans; D010446:Peptide Fragments; D010880:Piperidines; D000077265:Donepezil; D000109:Acetylcholine; D011188:Potassium