Douglas Institute. Canada: Imagine being able to easily get over all of the discomfort and
problems of jet lag or night-shift work. Science is not quite there, but
recent work by Marc Cuesta, Nicolas Cermakian and Diane B. Boivin from
the Douglas Mental Health University Institute and McGill University has
opened new therapeutic avenues for improving the synchronization of the
body's different biological clocks.
Physiological changes over the course of a day are regulated by a
circadian system comprised of a central clock located deep within the
centre of the brain and multiple clocks located in different parts of
the body.
This study, which was published in The FASEB Journal (published by
the Federation of American Societies for Experimental Biology), included
16 healthy volunteers who were studied in temporal isolation chambers.
These results show, for the first time, that the peripheral biological
clocks located in white blood cells can be synchronized through the
administration of glucocorticoid tablets.
Significant disruptions
Since humans are fundamentally diurnal creatures, staying awake at night
can significantly disrupt all of the body's internal biological clocks.
These disruptions are far from harmless: over the long term, they can
lead to a high incidence of various health problems, such as metabolic
or cardiovascular problems or even certain types of cancer.
“Problems adjusting to atypical work schedules are a major issue for
society. Our previous studies clearly show that desynchronized circadian
clocks disrupt the sleep, performance and cardiac parameters of
night-shift workers. However, current approaches to these problems have
significant limitations, as a single therapy can't address the
disruptions that occur in all biological clocks. For example, when used
incorrectly, light therapy can even aggravate the situation,” stated Dr.
Diane B. Boivin, Director of the Centre for Study and Treatment of
Circadian Rhythms, where the study took place.
Complex mechanisms
We still do not fully understand the mechanisms through which peripheral
biological clocks adapt to night-shift work in humans, but it is
thought that these clocks essentially depend on the central clock.
“Clock genes are what drive our biological clocks, and these genes are
active in all of our organs. Animal studies have shown that our central
clock (in the brain) sends signals to the clocks in our other organs.
Glucocorticoids appear to play a central role in transmitting these
signals. However, until now, no one had demonstrated that cortisol (a
glucocorticoid) plays this role in humans,” stated Dr. Nicolas
Cermakian, Director of the Laboratory of Molecular Chronobiology.
“We studied the rhythmic expression of clock genes in white blood cells
to see how they adjusted in response to glucocorticoids. These cells are
involved in our body's reaction to attacks from many pathogens. This
study therefore suggests that biological rhythms may play a role in
controlling immune function in night-shift workers,” added Dr. Marc
Cuesta, a postdoctoral fellow who works in the laboratories of Dr.
Boivin and Dr. Cermakian.
The previous work of Dr. Boivin and her team showed that exposing
workers to bright light at night tor adjusting work schedules can
improve the synchronisation of the central biological clock to their
atypical work schedule. This new scientific discovery opens the door to
innovative therapies that could act on the different parts of the
circadian system so that these rhythms can be adjusted to inverted sleep
schedules. These studies have possible applications for travellers,
night-shift workers, patients suffering from sleep disorders and
circadian rhythm disorders, as well as people with various psychiatric
disorders.
“At this stage, we are not recommending the use of glucocorticoids to
adjust the rhythms of night-shift workers, as there could be medical
risks,” explained Dr. Boivin. “However, these results lead us to believe
that we may one day be able to use a combined therapy that targets the
central clock (inverting work schedules, administering controlled light
therapy) with a pharmacological treatment that targets the peripheral
clocks to ensure that all clocks are adjusted.”
This research was funded by a grant from the Canadian Institutes of
Health Research (DBB, NC), funding from the Fonds de recherche Québec -
Santé (NC, MC), as well as support from the Standard Life .