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Sci Adv. 2017 Apr 5;3(4):e1602663. doi: 10.1126/sciadv.1602663. eCollection 2017 Apr.

Normal sleep requires the astrocyte brain-type fatty acid binding protein FABP7.

Author information

1
Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA.
2
Sleep and Performance Research Center, Washington State University, Spokane, WA 99210, USA.
3
Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
6
Department of Sleep and Behavioral Sciences, Shiga University of Medical Science, Otsu City, Shiga 520-2192, Japan.
7
Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
8
Department of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.

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. However, the role of FABP7 in regulating sleep remains poorly understood. We found that the missense mutation FABP7.T61M is associated with fragmented sleep in humans. This phenotype was recapitulated in mice and fruitflies bearing similar mutations: Fabp7-deficient mice and transgenic flies that express the FABP7.T61M missense mutation in astrocytes also show fragmented sleep. These results provide novel evidence for a distinct molecular pathway linking lipid-signaling cascades within astrocytes in sleep regulation among phylogenetically disparate species.

KEYWORDS:

B-FABP; BLBP; Evolution; astrocyte; gene; glia; missense; polymorphism; sleep; sleep fragmentation

PMID:
28435883
PMCID:
PMC5381954
DOI:
10.1126/sciadv.1602663
[Indexed for MEDLINE]
Free PMC Article

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