Rat Models of Age Related Cognitive Decline

Jennifer L. Bizon and Michelle M. Nicolle

Naturally occurring rat models can be useful for studying age-related cognitive decline. Long-Evans rats trained on the Morris water maze have been used to model individual differences in cognitive abilities that depend on the medial temporal lobe system. This approach has yielded a great deal of new information including the unexpected lack of neuronal loss in the hippocampus in aged rats with pronounced cognitive impairment. Despite this absence of neuron death, aged rats with impaired memory can be distinguished from those with intact memory at the neurobiological level. Cellular and molecular changes include alterations in the electrophysiological properties involved in synaptic plasticity, alterations in gene and protein expression, and efficacy of cell signaling pathways.

The prefrontal cortex and cognitive abilities supported by this brain region are also subject to age-related decline. The rat prefrontal cortex performs certain aspects of what is conventionally known as ''executive function'' in primates. This includes the ability to alter behavior in the face of changing environmental contingencies. Recently, an attentional set-shifting task has been designed for assessing executive function in rats. Individual differences in attentional set shifting have been described in aged rats, and this task is currently being combined with neurobiological studies to yield information regarding the underlying causes of behavioral impairment. The use of these two tasks assessing age-related cognitive impairment and the general approaches described in this chapter should yield informative data regarding our understanding of the neurobiology of age-related cognitive decline and should be useful for guiding therapeutic approaches targeting such deficits in humans.

Introduction

Age-related cognitive decline is a substantial problem, particularly based on the growing population of elderly in the United States and in other developed nations. The number of people over 65 living in the United States is expected to increase from 35 million in 2000 to

71.5 million by the year 2030, comprising almost 20% of the U.S. population (U.S. Census Bureau, 2004). It has further been estimated that 7-8% of individuals in the United States have severe cognitive impairment (Freedman et al., 2002). This cognitive disability contributes a significant burden with regard to reduced individual quality of life as well as financial strain on the healthcare system and society—a burden that can only be expected to escalate. Understanding neurobiological factors that contribute to cognitive decline with aging is the initial step in combating this health problem. Animal models of aging complement human studies and can be advantageous for investigating the neurobiol-ogical changes that underlie age-related cognitive decline. Ultimately, the use of animal models will contribute to the discovery of efficacious treatment options for humans with cognitive impairment.

Using Rats to Model Aging

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