Mice With a Genetic Vulnerability to Cognitive Impairment Show Greater Deficits With Aging in a Sex-Dependent Manner

2.50
Hdl Handle:
http://hdl.handle.net/10755/159199
Type:
Presentation
Title:
Mice With a Genetic Vulnerability to Cognitive Impairment Show Greater Deficits With Aging in a Sex-Dependent Manner
Abstract:
Mice With a Genetic Vulnerability to Cognitive Impairment Show Greater Deficits With Aging in a Sex-Dependent Manner
Conference Sponsor:Midwest Nursing Research Society
Conference Year:2007
Author:Hebda-Bauer, Elaine, PhD
P.I. Institution Name:University of Michigan
Contact Address:Molecular & Behavioral Neuroscience Institute, Ann Arbor, MI, 48103, USA
Co-Authors:J. Luo, S.J. Watson, and H. Akil, Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI
Age-related changes in the hippocampus increase vulnerability to impaired learning and memory (L&M). Our goal is to understand how a genetic vulnerability to cognitive impairment (CI) can be modified by gender and aging. Mice with a mutation in the cAMP response element binding (CREB) protein gene (CREB mice) are a model of mild CI and show test condition-dependent L&M. We tested 3 ages of CREB and wild type (WT) mice: young (2-4 mo. old), middle-aged (12-14 mo. old), and aged (22-24 mo. old) in the Morris water maze (MWM). Mice of each age, genotype, and sex were randomly assigned to 1 of 2 MWM protocols for 4 days. Mice received 2 trials/day with a 1-min inter-trial interval (ITI) in the MWM2, a task in which young CREB mice perform poorly, or 4 trials/day with a 3-5 min ITI in the MWM4, a task in which CREB mice perform well. Memory of all mice was tested 24 hrs later during a probe trial in which the escape platform was removed. Distance traveled to the goal and degree of search error, among other variables, were analyzed via 3 way (genotype, age, and sex) ANOVAs with repeated measures and posthoc analyses with specified contrasts. Among male CREB mice, the young had difficulty with the MWM2 task and probe trial as expected. Middle-aged CREB males performed well during the MWM2 but were impaired during the probe trial. Aged male CREB mice were very impaired during the MWM2 and the probe trial. In the easier MWM4 task, all 3 ages of male CREB mice performed well except for an early learning deficit in the middle-aged males and only a memory deficit in the probe trial for the aged males. Female CREB mice of all 3 ages were impaired in the MWM2 and probe trial. Unlike male CREB mice, only young female CREB mice performed well in the MWM4. Middle-aged CREB females in the MWM4 showed an early learning impairment and a memory deficit in the probe trial. Aged CREB females demonstrated very little learning across days in the MWM4 and impaired memory in the probe trial. These data show that mice with a genetic vulnerability to impaired L&M exhibit increased vulnerability with age that is most apparent among females. In conclusion, a genetic predisposition to CI may render females more vulnerable to such deficits with age.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Midwest Nursing Research Society

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleMice With a Genetic Vulnerability to Cognitive Impairment Show Greater Deficits With Aging in a Sex-Dependent Manneren_GB
dc.identifier.urihttp://hdl.handle.net/10755/159199-
dc.description.abstract<table><tr><td colspan="2" class="item-title">Mice With a Genetic Vulnerability to Cognitive Impairment Show Greater Deficits With Aging in a Sex-Dependent Manner</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Midwest Nursing Research Society</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2007</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">Hebda-Bauer, Elaine, PhD</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">University of Michigan</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">Molecular &amp; Behavioral Neuroscience Institute, Ann Arbor, MI, 48103, USA</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">hebda@umich.edu</td></tr><tr class="item-co-authors"><td class="label">Co-Authors:</td><td class="value">J. Luo, S.J. Watson, and H. Akil, Molecular &amp; Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI</td></tr><tr><td colspan="2" class="item-abstract">Age-related changes in the hippocampus increase vulnerability to impaired learning and memory (L&amp;M). Our goal is to understand how a genetic vulnerability to cognitive impairment (CI) can be modified by gender and aging. Mice with a mutation in the cAMP response element binding (CREB) protein gene (CREB mice) are a model of mild CI and show test condition-dependent L&amp;M. We tested 3 ages of CREB and wild type (WT) mice: young (2-4 mo. old), middle-aged (12-14 mo. old), and aged (22-24 mo. old) in the Morris water maze (MWM). Mice of each age, genotype, and sex were randomly assigned to 1 of 2 MWM protocols for 4 days. Mice received 2 trials/day with a 1-min inter-trial interval (ITI) in the MWM2, a task in which young CREB mice perform poorly, or 4 trials/day with a 3-5 min ITI in the MWM4, a task in which CREB mice perform well. Memory of all mice was tested 24 hrs later during a probe trial in which the escape platform was removed. Distance traveled to the goal and degree of search error, among other variables, were analyzed via 3 way (genotype, age, and sex) ANOVAs with repeated measures and posthoc analyses with specified contrasts. Among male CREB mice, the young had difficulty with the MWM2 task and probe trial as expected. Middle-aged CREB males performed well during the MWM2 but were impaired during the probe trial. Aged male CREB mice were very impaired during the MWM2 and the probe trial. In the easier MWM4 task, all 3 ages of male CREB mice performed well except for an early learning deficit in the middle-aged males and only a memory deficit in the probe trial for the aged males. Female CREB mice of all 3 ages were impaired in the MWM2 and probe trial. Unlike male CREB mice, only young female CREB mice performed well in the MWM4. Middle-aged CREB females in the MWM4 showed an early learning impairment and a memory deficit in the probe trial. Aged CREB females demonstrated very little learning across days in the MWM4 and impaired memory in the probe trial. These data show that mice with a genetic vulnerability to impaired L&amp;M exhibit increased vulnerability with age that is most apparent among females. In conclusion, a genetic predisposition to CI may render females more vulnerable to such deficits with age.</td></tr></table>en_GB
dc.date.available2011-10-26T21:47:53Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T21:47:53Z-
dc.description.sponsorshipMidwest Nursing Research Societyen_GB
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