Jet Lag Linked to the Lhx1 Gene

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Jet lag was linked to a single gene, specifically the Lhx1 gene, in a recent study. The significance of this discovery is that it offers a strategy for treatments of sleep disorders and jet lag problems that many people suffer from when travelling. The Lhx1 gene has been called a master gene responsible for controlling sleep and wake cycles.

Scientists at the Salk Institute for Biological Studies in La Jolla, California carried out the research on jet lag and the Lhx1 gene and the report on the study was published in the journal eLife. Satchidananda Panda was the lead scientist for the study.

Biological organisms have a circadian rhythm, sometimes called a biological rhythm or the circadian clock. This circadian rhythm results in a cycle of sleep and wakefulness that is approximately 24 hours in total. The changes in environmental light and darkness play a role in setting this internal circadian rhythm. The master circadian clock is in the brain and it is called the suprachiasmatic nucleus, or SCN. Light reaching the eye is processed in the retina and then these signals are sent to the brain where some of the information is sent down neural pathways that create visual perceptions but other pathways process the information to “set the circadian clock.” The SCN receives this information and then sends out directives to the body to create changes in hormone levels and nervous system functions in a cyclical 24 hour fashion. Much of the biochemistry in the body occurs in a cyclical manner and our sleep and wake states become cyclical as well.

When people travel, this circadian rhythm is affected and is said to be phase shifted. The day and night times are changed with travel and this affects how the circadian clock is set. People often feel jet lag when this happens. The feelings of jet lag are sluggishness and biochemical “fuzziness,” for example.

In the recent study, the Lhx1 gene was studied in mice who were subjected to disruptions in their light-dark cycles. The results showed that the mice with little or no Lhx1 protein adjusted much slower to phase shifts in the circadian rhythm compared with mice that had higher levels of this protein. The authors stated that they identified the Lhx1 gene as a regulator of SCN coupling, meaning the Lhx1 gene was shown to regulate the intercellular communication contributing to SCN functions. The results showed that a light pulse that phase-shifted the circadian rhythm caused acute reduction in the expression of Lhx1. Mice that lacked a Lhx1 gene were shown to have reduced SCN coupling factors and they entered a state of jet lag. Having a normal level of the Lhx1 protein was shown to create synchrony among the SCN neurons and produced consolidated rhythms of rest and activity.

The way that this information about the Lhx1 gene could be translated into therapy for jet lag and sleep disorders is a pill could be designed that could provide Lhx1 protein to someone in need. Increasing Lhx1 levels may help to adjust the circadian rhythm and restore proper sleep-wake cycles. This was the first study that showed a link between the Lhx1 gene and jet lag.

By Margaret Lutze

Salk News Release
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