Effects of Chronic Moderate Sleep Restriction and Exercise on Cancer, Anxiety-Related Behavior, and Memory of Mice
There has been speculation that chronic moderate sleep restriction is harmful to health in ways similar to the detriments of acute prolonged sleep deprivation. However, this hypothesis has not been tested experimentally. Exercise can be beneficial to health. The purpose of this dissertation was to examine the influence of chronic moderate sleep restriction and exercise on sleep, carcinogenesis, anxiety, and memory. In experiment 1, C57BL/6 mice were randomized to one of three 14-day treatments: (1) sleep restriction + sedentary; (2) normal sleep + exercise; (3) sleep restriction + exercise. Mice in the sleep restriction treatments were prevented from sleeping during the 12-hr dark period, while mice in the normal sleep treatment were allowed to sleep ad libitum. Mice in the exercise treatments ran on a treadmill at a moderate pace for 1 hr per day, whereas mice in the sedentary treatment did not run, but were handled similarly. Sleep restriction reduced daily sleep by ~ 4 hrs/day, but sleep restriction did not elicit a significant change in sleep during the light cycle nor in recovery sleep after the 14-day intervention. The normal sleeping + exercise treatment resulted in a modest increase in sleep time during the same dark period in which exercise occurred, but not in the subsequent light period, nor after the 14-day intervention. Sleep restriction + exercise modestly increased daily REM sleep times compared with the sleep restricted + sedentary treatment, but had had little other effect on sleep. In experiment 2, APC Min+/- mice, a genetic strain which develops colorectal cancer, were randomized to one of four 11-week treatments: (1) normal sleep + sedentary; (2) sleep restriction + sedentary; (3) normal sleep + exercise; (4) sleep restriction + exercise. Compared to normal sleep, sleep restriction increased polyp burden, and pro-inflammatory cytokine production of IL-1β and TNF-α. Exercise training resulted in reductions in polyp numbers and burden, and cytokine production (IL-1β, TNF-α, and IL-6) compared to sedentary control, although these benefits were reduced under chronic moderate sleep restriction. The sleep restriction and exercise treatments did not alter plasma corticosterone levels, suggesting that these effects were not due to stress. In experiment 3, C57BL/6 mice underwent the same treatments as the mice in experiment 2. Compared to controls, sleep restriction did not increase anxiety but resulted in impaired spatial memory acquisition and recall, and these changes coincided with significant reductions in hippocampal c-Fos and brain-derived neurotrophic factor. Exercise training resulted in a reduction in anxiety-related behavior and an improvement in memory acquisition and recall with corresponding increases in hippocampal c-Fos. SLEEP-by-ACTIVITY interactions revealed that the benefits of exercise on memory and c-fos were apparent under normal sleep, but not sleep restriction conditions. These data suggest that chronic moderate sleep restriction may reduce the potential benefits of exercise.
Exercise Science, Kinesiology, Life Sciences, anxiety, cancer, exercise, memory, sleep restriction
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