Scientists identify gene that regulates sleep patterns and wake -
Scientists at the Salk Institute for Biological Studies have identified a gene that regulates sleep patterns and awakening.
The discovery of the role of this gene, called LHX1, provides scientists with a potential therapeutic target to help night shift or hourly workers traveler accommodate time differences more quickly. The findings, published in eLife , can point to treatment strategies for sleep disorders caused by a variety of disorders.
"It is possible that the severity of dementia comes from many sleep disorders," says Satchidananda Panda, an associate professor who led the Salk research team. "If we can restore normal sleep, we can meet half the problem "
Each cell in the body has a" clock. "- an abundance proteins that plunge or rise rhythmically over about 24 hours the main clock responsible for the establishment. these cyclical circadian rhythms and keep all body cells in sync is the suprachiasmatic nucleus (SCN), a small region dense of about 20,000 neurons housed in the hypothalamus of the brain.
even more than in other brain regions, neurons in the SCN are in close and constant communication with each other. this close interaction, associated with exposure to light and darkness through the circuits of vision, maintains this master clock synchronization and allows people to stay on essentially the same program every day. The tight coupling of these cells also helps make collectively resistant to change. Exposure to light resets less than half of CNS cells, which leads to long periods of time difference.
In the new study, the researchers disrupted the light-dark cycles in mice and changes compared to the expression of thousands of genes in the SCN with other mouse tissues. They identified 213 changes in expression of genes that are unique to the RCS and shrunken in 13 thereof that encode the molecules that turn on and off of other genes. Among them, one was deleted in response to light :. LHX1
"Nobody ever imagined that LHX1 could be so closely involved in the SCN function," said Shubhroz Gill, a postdoctoral researcher and co-first author of the paper. LHX1 is known for his role in neuronal development: it is 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 the electrical activity in the SCN animals with reduced amounts of LHX1 protein, the researchers saw that the SCN neurons are not in phase with each other, despite appearing individually rhythm .
"It was all about communication, neurons were not talking to each other without this molecule," explains Ludovic Mure, a postdoctoral researcher and an author on the paper. The next stage of work will be to understand exactly how LHX1 affects the expression of genes that creates this synchronicity.
Consider a version of the mouse jet-lag one 8 hour shift in their day-night cycle scientists found that people with little or no LHX1 adjusted much quicker to change normal mice. This suggests that because these neurons are less in tune with each other, they are more easily able to move to a new calendar, but it is difficult for them to maintain this schedule, said Panda.
These mice also showed reduced activity of certain genes, including one that creates vasoactive intestinal peptide or VIP, a molecule that has an important role in the development and as a hormone in the intestine and blood. In the brain, affects cell Vip communication, but nobody knew LHX1 regulated until now, said Panda. Interestingly, the team also found that the addition Vip restored cell synchrony in the SNA.
"This approach has helped us to bridge this knowledge gap and show that Vip is a very important protein, at least for SCN," says Panda. "It can compensate the loss of LHX1."
Furthermore, cutting back on Vip might be another way to handle the schedule. Vip shift could be an even easier target of the drug compared to LHX1 because Vip is secreted from cells rather than cells inside, Panda said. "If we find a drug that will block the VIP receiver or somehow break Vip, so maybe that will help us reset the clock much faster," he added .
the new results take a little more of their target group to create cell regenerative therapies that restore the SNA and improve sleep problems. the scientists made their gene expression data available through a web interface available at http://scn.salk.edu, giving other researchers a convenient way to explore the effect of light and darkness in the genes of the SCN and other tissues.
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