期刊
NEUROBIOLOGY OF LEARNING AND MEMORY
卷 135, 期 -, 页码 73-82出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nlm.2016.07.001
关键词
Alzheimer's disease; Model mouse; Cognition; IntelliCage; Sex; Amyloid precursor protein
资金
- Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)
- Grants-in-Aid for Scientific Research [26290019] Funding Source: KAKEN
Transgenic mouse models of Alzheimer's disease (AD) with nonphysiologic overexpression of amyloid precursor protein (APP) exhibit various unnatural symptoms/dysfunctions. To overcome this issue, mice with single humanized App knock-in (KI) carrying Swedish (NL), Beyreuther/Iberian (F), and Arctic (G) mutations in different combinations were recently developed. The validity of these mouse models of AD from a behavioral viewpoint, however, has not been extensively evaluated. Thus, using an automated behavior monitoring system, we analyzed various behavioral domains, including executive function, and learning and memory. The App-KI mice carrying NL-G-F mutations showed clear deficits in spatial memory and flexible learning, enhanced compulsive behavior, and reduced attention performance. Mice carrying NL-F mutations exhibited modest abnormalities. The NL-G-F mice had a greater and more rapid accumulation of A beta deposits and glial responses. These findings reveal that single pathologic App-KI is sufficient to produce deficits in broad cognitive domains and that App-KI mouse lines with different levels of pathophysiology are useful models of AD. (C) 2016 The Author(s). Published by Elsevier Inc.
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