Female CREBalphadelta- deficient mice show earlier age-related cognitive deficits than males.
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.
Hebda-Bauer
E K
EK
Molecular and Behavioral Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI 48109, USA. hebda@umich.edu
Luo
J
J
Watson
S J
SJ
Akil
H
H
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D003072:Cognition Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D012727:Sex Characteristics
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D020033:Protein Isoforms