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- W2608367052 abstract "Sleep is found widely in the animal kingdom. Despite this, few conserved molecular pathways that govern sleep across phyla have been described. The mammalian brain-type fatty acid binding protein (Fabp7) is expressed in astrocytes, and its mRNA oscillates in tandem with the sleep-wake cycle. In this study, we examined whether Fabp7 is necessary for normal sleep/wake behavior in phylogenetically diverse species, including humans, mice, and the fruit fly, Drosophila melanogaster. Adult 2–4 month old male C57BL/6J wild-type (WT, N=7) mice were compared to age-matched isogenic Fabp7 knock-out (KO, N=8) mice using standard EEG/EMG techniques to examine sleep. Actigraphy measures of sleep in human adult male Fabp7 T61M mutant carriers (N=29) were compared to age-matched male non-carriers (N=265). The 7 day sleep profiles were assessed from the actigraphy records in conjunction with sleep diaries, and genotypes were blinded for the analysis. In order to test whether an astrocyte-specific functional Fabp7 is required for normal sleep in Drosophila, we generated transgenic flies that express either the human FABP7 WT (FABP7.WT, N=32) or FABP7 T61M (FABP7.T61M, N=27) under UAS-control, and used the Astrocyte-specific Alrm-GAL4 driver to control transgene expression. We measured sleep using the Drosophila Activity Monitoring System, and standard sleep scoring analytics. Fabp7 KO mice showed decreased average dark-phase NREM sleep bout duration (p<0.05) and an increase in the frequency of dark-phase NREM sleep bouts (p<0.05) compared to control mice. Increased frequency of dark-phase REM sleep bouts (p<0.05) was also observed. Humans which carry a Fabp7 Thr61Met missense mutation showed a decrease in average 7 d sleep bout duration (p<0.01) and an increase in the frequency of sleep bouts (p<0.05) compared to non-carriers. Similar to human FABP7 T61M carriers, the effects of FABP7.T61M in flies show increased sleep fragmentation compared to FABP7.WT flies. The FABP7.T61M flies had shorter bout durations (p<0.05), a reduction in the maximum sleep bout duration (p<0.05) and an increase in the frequency of sleep bouts (p<0.05). These results provide novel evidence for the astrocyte-specific gene, Fabp7, in regulating sleep across phylogenetically diverse species. MEXT KAKENHI 221S0002, NIH-HL007713, NIH-HL111725, NIH-MH099544, and ONR-N00014-13-1-0302." @default.
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- W2608367052 date "2017-04-28" @default.
- W2608367052 modified "2023-09-27" @default.
- W2608367052 title "0013 THE ASTROCYTIC FABP7 GENE REGULATES SLEEP ACROSS PHYLOGENY" @default.
- W2608367052 doi "https://doi.org/10.1093/sleepj/zsx050.012" @default.
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