Salk Institute for Biological Studies

Salk researchers discover a master gene responsible for sleep and wake cycles, offering hope for a drug that could help reset sleep

Scientists at the Salk Institute for Biological Studies have identified a gene that regulates sleep and wake rhythms.

The discovery of the role of this gene, called Lhx1, provides scientists with a potential therapeutic target to help night-shift workers or jet lagged travelers adjust to time differences more quickly. The results, published in eLife, can point to treatment strategies for sleep problems caused by a variety of disorders.

Its possible that the severity of many dementias comes from sleep disturbances, says Satchidananda Panda, a Salk associate professor who led the research team. If we can restore normal sleep, we can address half of the problem.

Every cell in the body has a clock an abundance of proteins that dip or rise rhythmically over approximately 24 hours. The master clock responsible for establishing these cyclic circadian rhythms and keeping all the bodys cells in sync is the suprachiasmatic nucleus (SCN), a small, densely packed region of about 20,000 neurons housed in the brains hypothalamus.

More so than in other areas of the brain, the SCNs neurons are in close and constant communication with one another. This close interaction, combined with exposure to light and darkness through vision circuits, keeps this master clock in sync and allows people to stay on essentially the same schedule every day. The tight coupling of these cells also helps make them collectively resistant to change. Exposure to light resets less than half of the SCN cells, resulting in long periods of jet lag.

In the new study, researchers disrupted the light-dark cycles in mice and compared changes in the expression of thousands of genes in the SCN with other mouse tissues. They identified 213 gene expression changes that were unique to the SCN and narrowed in on 13 of these that coded for molecules that turn on and off other genes. Of those, only one was suppressed in response to light: Lhx1.

No one had ever imagined that Lhx1 might be so intricately involved in SCN function, says Shubhroz Gill, a postdoctoral researcher and co-first author of the paper. Lhx1 is known for its role in neural development: its so important, that mice without the gene do not survive. But this is the first time it has been identified as a master regulator of light-dark cycle genes.

By recording electrical activity in the SCN of animals with reduced amounts of the Lhx1 protein, the researchers saw that the SCN neurons werent in sync with one another, despite appearing rhythmic individually.

Originally posted here:
Single Gene Provides A Potential Therapeutic Target To Help Night-Shift Workers Or Jet Lagged Travelers

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