Female CREBalphadelta- deficient mice show earlier age-related cognitive deficits than males.

Full Abstract

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(alphadelta-) deficient mice) have a mild cognitive impairment and show test condition-dependent learning and memory deficits. We tested three ages of CREB(alphadelta-) deficient and wild-type (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(alphadelta-) 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(alphadelta-) deficient mice performed well, but aged male and all middle-aged and aged female CREB(alphadelta-) 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.

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Author information

Author/s: Hebda-Bauer, E K (EK); Luo, J (J); Watson, S J (SJ); Akil, H (H);

Affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI 48109, USA. hebda(-atsign-)umich.edu

Grants: P01MH42251 (Agency:NIMH NIH HHS) ; R01DA3386 (Agency:NIDA NIH HHS) ; T32-DA07268 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Neuroscience (Neuroscience), published in United States. (Language: eng)

Reference: 2007-Dec; vol 150 (issue 2) : pp 260-72

Dates: Created 2007/12/10; Completed 2008/04/03; Revised 2008/11/20;

PMID: 18029102, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aging - genetics; metabolism
Animals
Brain - metabolism; physiopathology
Brain Chemistry - genetics
Cognition Disorders - genetics; metabolism; physiopathology
Cyclic AMP Response Element-Binding Protein - genetics
Disease Models, Animal
Disease Progression
Female
Genetic Predisposition to Disease - genetics

Genetic Predisposition to Disease - genetics
Male
Maze Learning - physiology
Memory Disorders - genetics; metabolism; physiopathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation - genetics
Protein Isoforms - genetics
Sex Characteristics

Associated Chemicals: Creb1 protein, mouse (0) ; Cyclic AMP Response Element-Binding Protein (0) ; Protein Isoforms (0)

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