期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 95, 期 8, 页码 1548-1564出版社
WILEY
DOI: 10.1002/jnr.23778
关键词
neurodegeneration; fruit fly; amyloid-
资金
- National Institutes of Health [T32 HL07713, T32 HL110952, P01AG017628]
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- (A) have been shown to be regulated by neuronal activity and to correlate with the sleep/wake cycle. Whether consolidated sleep can be disrupted by A alone is not well understood. We hypothesize that A42 can increase wakefulness and disrupt consolidated sleep. Here we report that flies expressing the human A42 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. A42 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 A42-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 A42-induced sleep loss will be important for the development of therapeutics in the treatment of AD. (c) 2016 Wiley Periodicals, Inc.
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