1. Amyloid-β induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila.
- Author
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Gerstner JR, Lenz O, Vanderheyden WM, Chan MT, Pfeiffenberger C, and Pack AI
- Subjects
- Animals, Animals, Genetically Modified, Disease Models, Animal, Drosophila, Drosophila Proteins genetics, Drosophila Proteins metabolism, Fatty Acid-Binding Proteins genetics, Gene Expression Regulation drug effects, Hormone Antagonists toxicity, Humans, Locomotion drug effects, Locomotion genetics, Mifepristone pharmacology, Mifepristone toxicity, RNA, Messenger metabolism, Sleep drug effects, Sleep genetics, Sleep Wake Disorders chemically induced, Sleep Wake Disorders physiopathology, Transcription Factors genetics, Transcription Factors metabolism, Wakefulness drug effects, Wakefulness genetics, Amyloid beta-Peptides genetics, Fatty Acid-Binding Proteins metabolism, Gene Expression Regulation genetics, Sleep Wake Disorders genetics
- Abstract
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., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2017
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