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

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

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.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Biological Clocks / physiology
  • Brain / cytology
  • Brain / metabolism*
  • Drosophila melanogaster
  • Fatty Acid-Binding Protein 7 / biosynthesis*
  • Fatty Acid-Binding Protein 7 / genetics
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Mutation, Missense
  • Signal Transduction / physiology*
  • Sleep / physiology*
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • FABP7 protein, human
  • Fabp7 protein, mouse
  • Fatty Acid-Binding Protein 7
  • Tumor Suppressor Proteins