The Role of CREB in Age-Related Changes in Sleep/Wake Patterns

University Of Pennsylvania, Philadelphia PA

Investigators

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Abstract

Sleep serves a number of functions, including memory storage and synaptic plasticity. One of the most prevalent complaints in the elderly is the dysregulation of sleep/wake patterns and daytime sleepiness. The goal of our research is to define how sleep is altered with age and to identify the molecular mechanisms underlying age-related deterioration of sleep/wake. Because aging is accompanied by alterations in both sleep and memory, defining the role of sleep may help us understand the behavioral, cellular and molecular changes that occur during aging and enable us to identify therapeutic approaches that might reverse these alterations. Aging is associated with increased sleep fragmentation, and the inability to sustain sleep/wake states. What are the underlying mechanisms of these disruptions? What are the consequences of these changes? How do these changes affect the function of sleep? The experiments in this project focus on the molecular and cellular mechanisms responsible for the dysregulation of sleep/wake in aged mice. Our work reveals that the CREB signaling pathway is required to promote and sustain wakefulness. Our proposed research begins by mapping where CREB is required to sustain wakefulness in the brain across the lifespan of mice (Specific Aim 1). We then examine where CREB signaling is reduced in aged animals and how these changes affect gene expression (Specific Aim 2). In Specific Aim 3, we attempt to rescue age- related fragmentation of sleep/wake by increasing CREB signaling in the brain. Together, the proposed experiments will define how sleep/wake patterns are altered by aging and will identify the molecular and cellular mechanisms underlying these age-related alterations in sleep/wake.