A RAT MODEL FOR SLEEP REGULATION DURING AGING

Brigham And Women'S Hospital, Boston MA

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Abstract

Older people have loss of about 30-50 minutes of sleep per day compared to young people and greater[unreadable] fragmentation of their remaining sleep. They subsequently are more sleepy during the day and nap more[unreadable] often. We hypothesize that this sleep-wake behavior pattern may be due to the loss of about 50% of the[unreadable] neurons in the ventrolateral preoptic nucleus (VLPO) by about 70 years of age. We plan to study the role of[unreadable] partial sleep restriction and fragmentation in older people with 50% VLPO cell loss in a rat model in which[unreadable] partial VLPO lesions will reduce the cell numbers in young (3 mo) and older (21 mo) rats to 50% of that in[unreadable] healthy young rats. In Aim 1, we will study the sleep-wake cycles of these animals with EEG/EMG and will[unreadable] determine the effect of short term acute sleep deprivation on recovery sleep. We predict that these animals,[unreadable] like older humans, will paradoxically tolerate sleep deprivation better than will young, intact animals. In Aim[unreadable] 2, we will examine the effects of chronic partial sleep restriction in young and older rats with 50% VLPO[unreadable] lesions, on performance in a memory test (Morris water maze) and coordination ,task (Rotarod). We predict[unreadable] that a large part of the fall-off in both memory and motor coordination with age will be due to sleep loss. We[unreadable] also expect that the animals with partial VLPO loss will have less impairment due to further acute sleep[unreadable] deprivation, as they will already be near the maximum level of the effect of cumulative sleep loss on[unreadable] cognitive and motor function. In Aim 3, we will examine the effects of chronic sleep restriction in both young[unreadable] and older rats on metabolic function (glucose, triglycerides, insulin, leptin, ghrelin levels) and immune[unreadable] function (interleukin-6, tumor necrosis factor alpha, C-reactive protein levels). We predict that the loss of[unreadable] sleep will cause changes consistent with the Metabolic Syndrome, such as seen in humans with sleep loss[unreadable] and with aging. Finally, in Aim 4 we will examine whether sleep repletion, using a drug that increases the[unreadable] firing of the remaining VLPO neurons, will reverse these deficits in cognitive, motor, metabolic, and immune[unreadable] function that are due to chronic partial sleep restriction. These data will allow us to establish a rat model for[unreadable] human sleep-wake deficits, and to determine the effect of those deficits on cognitive, motor, metabolic, and[unreadable] immune function, independent of age. If sleep repletion can reverse some of these deficits, such treatment[unreadable] may provide a way for improving both sleep and mental and physical health of older people.