A Mutated Gene Might Be Blocking You From a Good Night's Sleep

Scientists are one step closer to solving the mystery of why you just want more sleep.


If you can’t ever seem to nail a good night’s sleep, it might not be because of daylight saving time or questionable sleep apps or even evolution. It could just be that sound sleep is impossible due to a mutated gene in your brain, according to research published on Wednesday in Science Advances.

The protein gene, FABP7, affects not only how soundly humans sleep but mice and flies, too. Scientists found that humans with a mutated form of the gene were more likely to wake up during the night and sleep for shorter periods of time. Mice bred to not have the gene and flies that were genetically engineered to host a mutant form of FABP7 also slept less well than control subjects with the regular form of FABP7.

It’s the first time an astrocyte gene has been found to play a role in the regulation of sleep among such distinctly different species, suggesting FABP7 likely applies to most — if not all — animals.

“The cool thing about this is that sleep is such a ubiquitous behavior — you see it in all these species throughout the animal kingdom — but it turns out we still don’t know what sleep is doing,” co-author and research assistant professor Jason Gerstner tells Inverse. “To understand what its function is, an important first step for us as scientists is to look at the genes like FABP7, and identify mutations across different species so we can get a better understanding of sleep’s potential function.”

Professor Gerstner and Washington State University colleagues.

Cori Medeiros, WSU

When Gerstner was a graduate student at the University of Wisconsin, Madison, he was part of a team that found that FABP7, located in star-shaped cells called astrocytes, oscillated over time throughout the entire brain. Genes like this that cycle in the brain based on time of day are also responsible for the regeneration of circadian rhythms. And while scientists have known that astrocytes help the brain do things like deliver nutrients and kickstart injury repair, they didn’t know whether or not the protein genes in astrocytes would affect sleep cycles.

However, now that Gerstner and his team have carefully analyzed and monitored humans with naturally mutated forms of FABP7 as well as mice and flies engineered to carry the mutated protein gene, they are confident of its ties to having a good night’s sleep. Gerstner’s next step is to see whether or not this finding can be applied to a better understanding the relationship between sleep disturbance and neurodegenerative conditions like Alzheimer’s disease. Gerstner says that there appears to be a reciprocal relationship between disruptive sleep and Alzheimer’s disease pathology; understanding how a particular protein like FABP7 can help give scientists more clues to how longer periods of sleep can help delay disease progression.

“Not only does it appear that some of the disease associated agents responsible for Alzheimer’s disease seem to disrupt sleep, but in turn it also seems that disrupted sleep seems to exacerbate these disease-causing agents,” Gerstner tells Inverse. “A better understanding of how normal sleep is regulated is important for understanding how to treat something as complex as Alzheimer’s disease.”

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.
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