The overall goal of this program of research is to investigate the mechanisms of, and consequences from, changes with sleep in older animals. The studies extend to evaluating changes in sleep in animal models of neurodegenerative disease and the mechanisms for these changes. To accomplish these goals, the program has 4 projects and 3 cores. The first project (Project Leader: A. Sehgal) uses Drosophila, which is increasingly becoming a model to study sleep mechanisms and aging. This project brings these two lines of study together and we propose to investigate the changes with sleep across the lifespan in Drosophila, whether such changes are mediated by oxidative mechanisms, and whether reduction of sleep amounts influences lifespan. Project 02 (Project Leader: A.I. Pack) is directed at the molecular functions of sleep and whether these funds are impaired in older animals. These studies are done in mice. Specifically, the project looks at the changes with sleep and wakefulness in regulation of protein translation and cholesterol synthesis and the role of alteration of activity of the AMP-dependent kinase in controlling these processes. Another aspect of the function of sleep is investigated in Project 03 (Project Leader: T. Abel). Dr. Abel looks, in mice, at the role of sleep in memory and whether this effect is reduced in older animals. Studies are proposed to investigate both the cellular and molecular mechanisms involved. In the final project, Dr. S. Veasey (Project Leader) studies mouse models of Alzheimer's disease. She proposes to study alterations in sleep in these mice and to determine the relationship with specific mechanisms affecting neurons involved in sleep/wake control. These four projects are supported by 3 cores: (A) Administrative Core, (B) Behavioral Assessment Core, and (C) Biostatistical and Data Base Core. Thus, these studies are directed at a common problem in older adults, i.e., disruption of sleep. The studies are directed at determining what causes this disruption and, moreover, what its consequences are in terms of how the brain functions. Studies are also proposed to determine if cutting back on sleep affects how long you live and why sleep is particularly disturbed in Alzheimer's disease. These studies have the potential to open up new avenues for treatment of sleep disruption in older adults.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-2 (O1))
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Wise, Bradley C
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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Zimmerman, John E; Chan, May T; Lenz, Olivia T et al. (2017) Glutamate Is a Wake-Active Neurotransmitter in Drosophila melanogaster. Sleep 40:
Anafi, Ron C; Francey, Lauren J; Hogenesch, John B et al. (2017) CYCLOPS reveals human transcriptional rhythms in health and disease. Proc Natl Acad Sci U S A 114:5312-5317
Gerstner, Jason R; Lenz, Olivia; Vanderheyden, William M et al. (2017) Amyloid-? induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila. J Neurosci Res 95:1548-1564
Havekes, Robbert; Abel, Ted (2017) The tired hippocampus: the molecular impact of sleep deprivation on hippocampal function. Curr Opin Neurobiol 44:13-19
Morgan, Andrew P; Gatti, Daniel M; Najarian, Maya L et al. (2017) Structural Variation Shapes the Landscape of Recombination in Mouse. Genetics 206:603-619
Gardner, Benjamin; Strus, Ewa; Meng, Qing Cheng et al. (2016) Sleep Homeostasis and General Anesthesia: Are Fruit Flies Well Rested after Emergence from Propofol? Anesthesiology 124:404-16
Havekes, Robbert; Park, Alan J; Tolentino, Rosa E et al. (2016) Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory. J Neurosci 36:8936-46
Havekes, Robbert; Park, Alan J; Tudor, Jennifer C et al. (2016) Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1. Elife 5:
Tudor, Jennifer C; Davis, Emily J; Peixoto, Lucia et al. (2016) Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis. Sci Signal 9:ra41
Perron, Isaac J; Pack, Allan I; Veasey, Sigrid (2015) Diet/Energy Balance Affect Sleep and Wakefulness Independent of Body Weight. Sleep 38:1893-903

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