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Establishing a rodent (Fischer 344 rat) model of mild cognitive impairment in aging

Mild Cognitive Impairment is characterized by age-related decline in a
variety of cognitive domains, including reference and working memory and
olfactory function. Importantly, declining age-related mnemonic abilities is not
inevitable; learning and memory deficits emerge in some people by middle-age
while others remain largely cognitively-intact even at advanced chronological
ages. The goal of this thesis is to establish a Fischer 344 (F344) rat model with
some features of human cognitive aging which can then be utilized to
undercover the neurobiological underpinnings of age-related cognitive deficits.
Young (6 mo), middle-aged (11 mo), and aged (22 mo) F344 rats were
behaviorally characterized in a well-established reference memory version of the
Morris water maze task. Indeed, age-related impairments did occur across the
lifespan. Moreover, the reference memory protocol used here was sufficiently
sensitive to detect a difference in individual abilities among aged F344 rats such
that approximately half of the rats performed on par with young while the other
half performed outside this range, demonstrating impairment. These data mimic
individual differences in declarative memory among aged humans. Subsequently, subsets of rats initially characterized on the reference memory
version of the water maze were tested on either a spatial working memory water
maze task or an olfactory discrimination task. Despite detecting an age-related
delay-dependent decline in spatial working memory, this impairment was not
correlated with spatial reference memory. In contrast, a strong and significant
relationship was observed among aged rats in the odor discrimination task such
that aged rats with the worst spatial reference memory were also the most
impaired in their ability to discriminate odors for a food reward. Importantly, this
subset of cognitively-impaired rats was not impaired on digging media
discrimination problems with identical task demands, nor were they anosmic.
These data are among the first to demonstrate a cross-domain cognitive
deficit in a rodent model of human aging. Together, the current study both
confirms the use of the naturalistic F344 rat model for the study of cognitive
deficits within the context of aging and provides the most comprehensive
cognitive profile of this rat population to date.
Date15 May 2009
CreatorsLaSarge, Candi Lynn
ContributorsBizon, Jennifer Lynn
Source SetsTexas A and M University
Detected LanguageEnglish
TypeBook, Thesis, Electronic Thesis, text
Formatelectronic, application/pdf, born digital

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