Microglia response to chronic sleep restriction

Chronically insufficient sleep is common in our society and is increasingly recognized as a cause of health and safety problems with significant economic costs. We only have a limited understanding of the mechanisms underlying the health and cognitive impairments associated with chronic sleep loss. It is crucial to develop improved strategies to deal with these negative consequences by understanding the mechanisms underlying impaired health due to chronic sleep loss. Towards this goal, we have developed a rat model of chronic sleep restriction. Our recent findings show that 4 days of insufficient sleep activates microglia (immune cells in the brain) and that this activation persists for at least one week following sleep loss. We propose to use this model to examine the mechanisms underlying the effects of chronic sleep loss, with a focus on the role, if any, of microglia. As there can be sex differences, we will use both male and female rats. To examine whether microglia activation is involved in the changes in sleep patterns observed during chronic sleep restriction, microglia will be inhibited using an antibiotic that blocks microglia functions, and sleep patterns will be recorded. We will also assess the response of microglia to chronic sleep loss and examine the anatomical relationship between microglia and neurons involved in sleep regulation after chronic sleep loss. In addition, we will determine whether chronic sleep loss sensitizes microglia to produce an exaggerated immune response in the brain to inflammatory stimuli that are subsequently administered. Insights gained from the proposed research could have significant health and economic impacts since sleep is so important, yet so often sacrificed for other activities. Ultimately, the proposed research will help us develop innovative strategies for coping with the negative impacts of reduced sleep and help reduce the adverse impacts of chronic sleep loss on the health of both men and women.