期刊
NEUROBIOLOGY OF AGING
卷 62, 期 -, 页码 120-129出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2017.10.013
关键词
Cognitive aging; Pattern separation; Object location; Object feature; D-serine
资金
- RMT-TMO Offensive Science initiative
- INTERREG IV Upper Rhine program (EU) [A29]
- France Alzheimer Association (APP SM, Groupe Interiale) [104]
- Neurex (Young Investigator Grant)
- University of Strasbourg
- Centre National de la Recherche Scientifique (CNRS)
Aging is associated with impaired performance in behavioral pattern separation (PS) tasks based on similarities in object features and in object location. These deficits have been attributed to functional alterations in the dentate gyrus (DG)-CA3 region. Animal studies suggested a role of adult-born DG neurons in PS performance. The present study investigated the effect of aging in C57BL/6J mice performing PS tasks based on either object features or object location. At the age of 18 months or more, performance was severely impaired in both tasks. Spatial PS performance declined gradually over adult lifespan from 3 to 21 months. Subchronic treatment with the cognitive enhancer D-serine fully rescued spatial PS performance in 18-month-old mice and induced a modest increase in the number of 4-week-old adult-born cells in the DG. Performance of mice in these PS tasks shows an age dependence, which appears to translate well to that found in humans. This model should help in deciphering physiological changes underlying PS deficits and in identifying future therapeutic targets. (C) 2017 Elsevier Inc. All rights reserved.
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