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

Area of Science:

• Neuroscience
• Molecular Biology
• Chronobiology

Background:

• Sleep is a fundamental biological process conserved across the animal kingdom.
• However, conserved molecular mechanisms regulating sleep across diverse phyla remain largely undescribed.
• The mammalian brain-type fatty acid binding protein (Fabp7), expressed in astrocytes, shows mRNA oscillation linked to the sleep-wake cycle, but its function in sleep is unclear.

Purpose of the Study:

• To investigate the role of mammalian brain-type fatty acid binding protein (Fabp7) in sleep regulation.
• To determine if mutations in Fabp7 are associated with sleep fragmentation.
• To explore the conservation of Fabp7-mediated sleep regulation across different species.

Main Methods:

• Human genetic association study to identify mutations linked to fragmented sleep.
• Generation and analysis of Fabp7-deficient mice.
• Creation of transgenic fruitflies expressing a specific Fabp7 missense mutation (FABP7.T61M) in astrocytes.
• Phenotypic analysis of sleep patterns in all models.

Main Results:

• A specific missense mutation, FABP7.T61M, was found to be associated with fragmented sleep in humans.
• Fabp7-deficient mice exhibited fragmented sleep patterns.
• Transgenic fruitflies expressing the FABP7.T61M mutation in astrocytes also displayed fragmented sleep.
• These findings were consistent across species, indicating conserved mechanisms.

Conclusions:

• Fabp7 plays a crucial role in regulating sleep consolidation.
• A conserved molecular pathway involving lipid-signaling cascades within astrocytes is implicated in sleep regulation.
• This pathway is evolutionarily conserved across phylogenetically disparate species, including mammals and insects.