期刊
NEUROSCIENCE
卷 150, 期 2, 页码 260-272出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2007.09.019
关键词
aging; sex differences; spatial; learning; memory; Morris water maze
资金
- NIDA NIH HHS [T32-DA07268, T32 DA007268-12, R01 DA013386-03, R01 DA013386-04, T32 DA007268, R01DA3386, R01 DA013386-01A2, R01 DA013386-02, R01 DA013386, T32 DA007268-13, R01 DA013386-05] Funding Source: Medline
- NIMH NIH HHS [P01 MH042251, P01MH42251, P01 MH042251-160012] Funding Source: Medline
Age-related changes in the hippocampus increase vulnerability to impaired learning and memory. Our goal is to understand how a genetic vulnerability to cognitive impairment can be modified by aging and sex. Mice with a mutation in the cAMP response element binding (CREB) protein gene (CREB alpha delta- deficient mice) have a mild cognitive impairment and show test condition-dependent learning and memory deficits. We tested three ages of CREB alpha delta- deficient and wildtype (WT) mice in two Morris water maze (MWM) protocols: four trials per day with a 3-5 min inter-trial interval (ITI) (MWM4) and two trials per day with a 1 min ITI (MWM2). All CREB alpha delta- deficient mice performed well in the easier MWM4, except for the aged females that performed poorly. In the harder MWM2, young male and female and middle-aged male CREB alpha delta- deficient mice performed well, but aged male and all middle-aged and aged female CREB alpha delta- deficient mice were impaired. These results show that mice with a genetic vulnerability to impaired learning and memory exhibit increased vulnerability with age that is most apparent among females. Thus, a genetic predisposition to cognitive impairment may render females more vulnerable than males to such deficits with age. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
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