Spatial memory impairment without apoptosis induced by the combination of beta-amyloid oligomers and cerebral ischemia is related to decreased acetylcholine release in rats

Takuya Watanabe, Katsunori Iwasaki, Shin Ishikane, Tetsuya Naitou, Yoshitaka Yoshimitsu, Norito Yamagata, Mehmeto Bülent Ozdemir, Kotaro Takasaki, Nobuaki Egashira, Kenichi Mishima, Michihiro Fujiwara

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)84-91
Number of pages8
JournalJournal of Pharmacological Sciences
Volume106
Issue number1
DOIs
Publication statusPublished - 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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