Spatial Memory Impairment Without Apoptosis Induced by the Combination of Beta-Amyloid Oligomers and Cerebral Ischemia Is Related to Decreased Acetylcholine Release in Rats

Journal of Pharmacological Sciences

Katsunori Iwasaki¹  Kotaro Takasaki¹  Michihiro Fujiwara¹  Tetsuya Naitou¹  Mehmeto Bülent Ozdemir¹  Nobuaki Egashira¹  Takuya Watanabe¹  Yoshitaka Yoshimitsu¹  Kenichi Mishima¹  Shin Ishikane¹  Norito Yamagata¹ 

[1] Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan

关键词: Alzheimer’s disease;    oligomer;    acetylcholine;    memory impairment;    behavior;   

DOI  :  10.1254/jphs.FP0071648

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(16)The purpose of the present study was to examine the effect of beta-amyloid (Aβ) oligomers, not the fibrils that make up Aβ plaques, on spatial memory and the cholinergic system in rats. Recently, several researchers have suggested that small assemblies of Aβ, Aβ oligomers, caused memory loss during the early stages of Alzheimer’s disease without showing cell death. In the present study, the combination of Aβ 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 Aβ oligomers and cerebral ischemia; however, high K+-evoked ACh release was decreased. These results suggest that a combination of Aβ 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.

【 授权许可】

Unknown