Amyloid-β induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila

Jason R Gerstner; Olivia Lenz; William M Vanderheyden; May T Chan; Cory Pfeiffenberger; Allan I Pack

doi:10.1002/jnr.23778

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Amyloid-β induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila

Journal article

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Amyloid-β induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila

Jason R Gerstner, Olivia Lenz, William M Vanderheyden, May T Chan, Cory Pfeiffenberger and Allan I Pack

Journal of neuroscience research, Vol.95(8), pp.1548-1564

08/2017

DOI: https://doi.org/10.1002/jnr.23778

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https://hdl.handle.net/2376/115858

PMCID: PMC5167666

PMID: 27320125

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https://doi.org/10.1002/jnr.23778View

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Abstract

Wakefulness - drug effects

Locomotion - genetics

Sleep Wake Disorders - chemically induced

Humans

Fatty Acid-Binding Proteins - metabolism

Drosophila Proteins - metabolism

RNA, Messenger - metabolism

Sleep Wake Disorders - genetics

Amyloid beta-Peptides - genetics

Sleep Wake Disorders - physiopathology

Disease Models, Animal

Locomotion - drug effects

Animals, Genetically Modified

Gene Expression Regulation - genetics

Wakefulness - genetics

Drosophila

Sleep - genetics

Transcription Factors - genetics

Fatty Acid-Binding Proteins - genetics

Sleep - drug effects

Gene Expression Regulation - drug effects

Transcription Factors - metabolism

Animals

Mifepristone - toxicity

Hormone Antagonists - toxicity

Drosophila Proteins - genetics

Mifepristone - pharmacology

Disruption of sleep/wake activity in Alzheimer's disease (AD) patients significantly affects their quality of life and that of their caretakers and is a major contributing factor for institutionalization. Levels of amyloid-β (Aβ) have been shown to be regulated by neuronal activity and to correlate with the sleep/wake cycle. Whether consolidated sleep can be disrupted by Aβ alone is not well understood. We hypothesize that Aβ42 can increase wakefulness and disrupt consolidated sleep. Here we report that flies expressing the human Aβ42 transgene in neurons have significantly reduced consolidated sleep compared with control flies. Fatty acid binding proteins (Fabp) are small hydrophobic ligand carriers that have been clinically implicated in AD. Aβ42 flies that carry a transgene of either the Drosophila Fabp or the mammalian brain-type Fabp show a significant increase in nighttime sleep and long consolidated sleep bouts, rescuing the Aβ42-induced sleep disruption. These studies suggest that alterations in Fabp levels and/or activity may be associated with sleep disturbances in AD. Future work to determine the molecular mechanisms that contribute to Fabp-mediated rescue of Aβ42-induced sleep loss will be important for the development of therapeutics in the treatment of AD. © 2016 Wiley Periodicals, Inc.

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Title: Amyloid-β induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila
Creators: Jason R Gerstner - Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington
Olivia Lenz - Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
William M Vanderheyden - Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington
May T Chan - Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Cory Pfeiffenberger - Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Allan I Pack - Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Publication Details: Journal of neuroscience research, Vol.95(8), pp.1548-1564
Academic Unit: Biomedical Sciences, Department of
Publisher: United States
Grant note: P01 AG017628 / NIA NIH HHS T32 HL110952 / NHLBI NIH HHS T32 HL007713 / NHLBI NIH HHS
Identifiers: 99900548140201842
Language: English
Resource Type: Journal article