A gene, Lhx1, which regulates sleep and wake patterns has been identified by scientists.
This discovery opens the door to the development of therapy to aid night-shift workers or travellers who suffer with jet lag, as it will allow them to adjust to time differences.
The body works on a clock and each cell has a range of proteins that go up and down during this period. The main clock for controlling these rhythms is the suprachiasmatic nucleus (SCN), which is a small region containing about 20000 neurons which are based in the hypothalamus of the brain.
The neurons maintain constant and close communication with each other. This tight interaction, along with light and darkness exposure via the vision circuits, maintains the synchronisation of the master clock which allows people to keep to the same schedule on a daily basis. The closeness of the cells makes them very change-resistant. Light exposure results in half of the SCN cells being reset, which results in long periods of jet lag.
During the new study, researchers disrupted the light and dark cycles in mice and the changes in the SCN gene expressions were compared with other tissues in the mice. They discovered 213 gene expression changes unique to the SCN and focused on 13 which they found could switch on and off other genes. Of these 13, only one was curbed when light was switched on. This was the Lhx1.
Lhx1 is known to be crucial in neural development. Its importance is so great that mice that do not have the gene are unable to survive. However, this is the first instance where it has been identified as a regulator of dark-light cycles genes.
The scientists recorded electrical activity in the SCN of mice with reduced quantities of the Lhx1 protein. During this activity the SCN neurons were not in sync with each other although individually they were in rhythm.
A researcher stated that it was linked to communication as the neurons were unable to communicate without the molecule.
By studying a version of jet-lag in a mouse by using an 8-hour shift in their normal day-night cycle, the scientists discovered that with a small amount or no Lhx1, they readjusted to a normal shift much quicker. The researchers state it indicates that because the synchronisation of the neurons has lessened, they have the ability to move to a new schedule, even though it is difficult to maintain that schedule.
The mice exhibited reduced activity in other genes, including the one which is responsible for the creation of vasoactive intestinal peptide (Vip). This is a molecule which plays a huge role in development and as a blood and intestine hormone. It affects communication between cells, but it was unknown that it was regulated by Lhx1. The team also discovered that by adding Vip the cell synchronisation in the SCN could be restored.
The leader of the team and associate professor at Salk Institute for Biological Studies, Satchidananda Panda, said the method they used aided them in closing the knowledge gap and showing that Vip is an important protein for SCN. Panda said it is able to compensate for the loss of Lhx1.
He said that cutting back on Vip could be an alternative method of treating jet lag. He added that Vip may be an easier drug target than Lhx1 as it is secreted from cells instead of inside cells. He said that finding a drug which will block the Vip receptor and break down Vip will aid in resetting the body clock quicker.
These new results have brought the group a step closer to their main aim of creating cell regenerative therapies which will restore SCN and alleviate sleep problems.
Image Credit: Bradley Gordon