In a new mouse study, scientists have discovered the gene that controls the body clock, and that faults in this gene can effectively “short circuit” circadian rhythms.
The gene in question, zinc finger homeobox 3 (Zfhx3), is highly active in the hypothalamus – an area of the brain that is responsible for the production of several important hormones.
Published in Cell, the study’s findings could explain why the body clock remains so consistent and why the irregular hours of shift work can have such a negative effect on employees’ health.
Previously, Medical News Today ran a Spotlight investigating the impact of shift work on health, examining how disruption to the body clock can cause sleep problems and potentially increase the prevalence of certain diseases.
“We’ve known for some time that upsetting the body clock isn’t good for us but this study takes us a lot closer to understanding the mechanism of that clock,” states study co-author Dr. Michael Hastings, a researcher at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK.
The body clock is also referred to as the circadian clock or cycle. It is a cycle lasting roughly the length of a day that controls the timing of several crucial biological processes such as sleep, hormone production and body temperature regulation. These processes that regularly change over the course of the day are known as circadian rhythms.
Although these processes are in part managed by cells within corresponding tissues, for all of the processes across the body to synchronize, there needs to be a centralized point to co-ordinate everything. This point is a small region of the hypothalamus called the suprachiasmatic nucleus (SCN).
Study authors investigated mice with a ‘short circuit’ body clock
To learn more about the workings of the body clock, the researchers compared the genes of mice with abnormally short body clocks with a control group with normal circadian rhythms. It was during this comparison that the researchers discovered Zfhx3 plays a much more prominent role than previously understood.
Although Zfhx3 had never been considered to be a part of the body clock, the researchers were able to demonstrate that it regulates the expression of important neurotransmitters (neuropeptides) and receptors that are crucial to the work of the SCN in synchronizing circadian rhythms.
In the mice, faults in the Zfhx3 gene led to miscommunication between cells in this area of the brain, in turn causing the biological clocks of the mice to be much faster than normal.
Lead researcher Dr. Pat Nolan says:
“Our discovery of this gene fault that speeds up the circadian rhythm of mice provides a valuable insight into how the body clock is controlled. This approach has allowed us to gain insight into how the regulation of neuropeptide networks in the hypothalamus can synchronize biological clocks in the whole organism.”
Being unable to synchronize biological rhythms within the brain has previously been associated with various behavioral and psychiatric disorders such as schizophrenia. Dr. Hastings states that their findings help explain why work patterns that force people to work against the synchronization of their body clock could lead to mental health and psychiatric disease.
“The success of this project highlights the enormous potential of using approaches based on mouse genetics to understand brain function and provides answers we could not get in other ways,” he concludes.
Earlier this year, another group of scientists was successful in identifying the key cells in the SCN that are critical in determining circadian rhythms.
Written by James McIntosh