Date Available

12-5-2013

Year of Publication

2013

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Medicine

Department/School/Program

Molecular and Biomedical Pharmacology

First Advisor

Dr. Eric Blalock

Abstract

Changes in both sleep architecture and cognition are common with age. Typically these changes have a negative connotation: sleep fragmentation, insomnia, and deep sleep loss as well as forgetfulness, lack of focus, and even dementia and Alzheimer’s disease. Research has shown that psychosocial stressors, such as isolation from family and friends or loss of a loved one can also have significant negative effects on sleep architecture and cognitive capabilities. This leaves the elderly in a particularly vulnerable situation: suffering from cognitive decline and sleep dysregulation already, and more likely to respond negatively to psychosocial stressors. Taking all of these factors into account, it’s surprising that little research has been done to elucidate the mechanisms behind aged subjects’ enhanced vulnerability to new onset psychosocial stress.

Our lab embarked on a series of studies to test the effects of age and psychosocial stress on sleep architecture and cognition. Our first study measured sleep stages in young adult and aged F344 rats during their resting and active periods. Animals were behaviorally characterized on the Morris water maze and gene expression profiles of their parietal cortices were taken. We confirmed previous studies that found impaired cognition and decreased resting deep sleep with age. However, it was increased active deep sleep that correlated best with poor cognitive performance. In the second study rats were subjected to immobilization (restraint stress) immediately preceding their final water maze task. Hippocampi were prepared for synaptic electrophysiology and trunk blood was taken for corticosterone measurement after post-stress sleep architecture data was collected. Young subjects responded to acute stress with decreased cognition, elevated CORT levels and altered sleep architecture. In contrast, stressed aged subjects were statistically indistinguishable from control aged subjects, suggesting that aged rats are less responsive to an acute psychosocial stress event. Together, these studies suggest that alleviating sleep dysregulation could therapeutically benefit cognition psychosocial stress resilience.

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