PMID: 18187922Jan 12, 2008Paper

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
Takuya WatanabeM Fujiwara

Abstract

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.

References

Dec 1, 1980·Journal of Neuroscience Methods·G PaxinosP C Emson
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·A Lorenzo, B A Yankner
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·K HensleyD A Butterfield
Mar 12, 1997·JAMA : the Journal of the American Medical Association·D A SnowdonW R Markesbery
Sep 18, 1997·Journal of Neuropathology and Experimental Neurology·M C IrizarryB T Hyman
Mar 16, 2001·Trends in Neurosciences·W L KleinC E Finch
May 4, 2002·Stroke; a Journal of Cerebral Circulation·Hayrunnisa BolayTurgay Dalkara
Jun 12, 2002·The Journal of Biological Chemistry·Karie N DahlgrenMary Jo LaDu
Aug 28, 2002·Biochemical Society Transactions·D M WalshD J Selkoe
Dec 26, 2002·Japanese Journal of Pharmacology·Nobuaki EgashiraMichihiro Fujiwara
Apr 30, 2003·The Journal of Biological Chemistry·Yuji YoshiikeAkihiko Takashima
Sep 29, 2004·Trends in Biochemical Sciences·Charles G Glabe
Dec 21, 2004·Nature Neuroscience·James P ClearyKaren H Ashe
Jul 26, 2006·The Journal of Biological Chemistry·Brent L Kelly, Adriana Ferreira
Apr 6, 2007·Biological & Pharmaceutical Bulletin·Katsunori IwasakiMichihiro Fujiwara

❮ Previous
Next ❯

Citations

Jan 5, 2011·International Journal of Alzheimer's Disease·E I ZakharovaA A Kubatiev
Sep 25, 2008·Cellular and Molecular Neurobiology·Elena I SolntsevaVladimir G Skrebitsky
Feb 4, 2010·Journal of Neuroscience Research·Takuya WatanabeMichihiro Fujiwara
Dec 25, 2010·Journal of Magnetic Resonance Imaging : JMRI·Ihssan A Abdul-KareemVanessa Sluming
May 27, 2011·Journal of Pharmacological Sciences·Kotaro TakasakiKatsunori Iwasaki

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis