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Dynamin 1 depletion and memory deficits in rats treated with Aβ and cerebral ischemia
Author(s) -
Watanabe Takuya,
Iwasaki Katsunori,
Takasaki Kotaro,
Yamagata Norito,
Fujino Mutsumi,
Nogami Ai,
Ii Miyuki,
Katsurabayashi Shutaro,
Mishima Kenichi,
Fujiwara Michihiro
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22346
Subject(s) - dynamin , ischemia , neuroscience , medicine , anesthesia , psychology , receptor , endocytosis
Alzheimer's disease (AD) is progressive dementia with senile plaques composed of β‐amyloid (Aβ). Recent studies suggest that synaptic dysfunction is one of the earliest events in the pathogenesis of AD. Here we provide the first experimental evidence that a change in the level of dynamin 1 induced by Aβ correlates with memory impairment in vivo. We treated rats with transient cerebral ischemia with oligomeric forms of Aβ (Aβ oligomers), including dimers, trimers, and tetramers, intracerebroventricularly. The combination of Aβ oligomers and cerebral ischemia, but not cerebral ischemia alone, significantly impaired memory and decreased the level of dynamin 1, which plays a critical role in synaptic vesicle recycling, but did not affect the levels of other synaptic proteins, such as synaptophysin and synaptobrevin, in the hippocampus. Furthermore, the N ‐methyl‐ D ‐aspartate (NMDA) receptor antagonist memantine prevented memory impairment and dynamin 1 degradation, suggesting that these changes might be mediated by NMDA receptors. These results suggest that Aβ oligomers induce memory impairment via dynamin 1 degradation, which may imply that dynamin 1 degradation is one of the causes of synaptic dysfunction in AD. © 2010 Wiley‐Liss, Inc.