Constant light has long been understood to disrupt our internal clocks,
resulting in problems like jet lag and health problems in
extended-shift workers. A study led by Vanderbilt researcher Douglas
McMahon reveals that although the clocks of individuals exposed to
constant light may get out of synch, they keep ticking. The findings
offer insight into how to modify constant-light situations to lessen
their impact on humans.
The research was published online Feb. 23 in the journal Nature Neuroscience.
“This inspires a very different approach if you are putting someone in
constant light, such as a neonatal intensive care unit or an extended
space mission,” McMahon, professor of biological sciences and an
investigator in the Vanderbilt Kennedy Center for Research on Human
Development, said. “Knowing that cellular clocks keep ticking means
that you can work on keeping them synchronized rather than restarting
them.”
Maintaining synchronization of our internal biological clocks has
important health consequences. For example, babies held in the neonatal
intensive care unit under constant dim light can show lower weight gain
than those on a more natural light cycle. Repeated jet lag can also
have adverse health effects.
McMahon said some methods for keeping biological clocks synchronized
are exercise, keeping an individual alert and exerting oneself, all of
which appear to provide feedback to the clock. This feedback has been
shown in studies in mice to reinforce natural rhythms and keep clocks
in synch.
“That kind of external reinforcement from another stimulus besides
light might be enough to keep clocks synchronized,” McMahon said.
Biological clocks are responsible for maintaining circadian rhythms,
which affect our sleep, performance, mood and more. The mammalian
biological clock in the brain is made up of multiple nerve cells, each
with a pair of identical nuclei.
McMahon and his colleagues,
post-doctoral researcher Hidenobu Ohta and Research Assistant Professor
Shin Yamazaki, set out to uncover what happens at the molecular level
when an individual is exposed to constant light.
“We wanted to be able to track not just the average activity of the
clock nuclei as a whole, but the individual cell rhythms and correlate
that with the behavior of an individual animal,” McMahon said. “Has the
light stopped the clocks in individual cells, or has it reorganized the
neurons?”
To answer this question, McMahon and his colleagues developed a method
to tag the activity of one of the clock activity-generating genes in
mice with a green fluorescent protein. The protein glowed in proportion
to how strongly the gene was being expressed throughout the day,
enabling the researchers to read the time on the molecular clocks.
The researchers found two different answers to their question,
depending upon the subject. Some animals experienced disruptions to
their behavior, while others seemed to adapt by creating a new internal
12-hour “day” during which they had active periods. For the animals
whose behavior was disrupted, the researchers found the clocks in
individual cells were still ticking, but they had become
desynchronized.
“Light had disrupted the communication mechanisms between cells that
keep them in synch,” McMahon said.
In the animals that exhibited the 12-hour cycle, the two identical
nuclei no longer beat together, but instead showed an alternating burst
of activity in the left and the right nucleus every 12 hours.
“The individual cell clocks had not stopped, but they had become
desynchronized. Some mechanism that couples the two sides was
disrupted. It appears that the nucleus on each side can control
behavior,” McMahon said.
Video illustrating the alternating bursts of activity in the left and
right nucleus is available online:
http://vvrc.vanderbilt.edu/NatNeurosci2005OhtaYamazakiMcMahon/S3.mov.
The work was supported by a grant from the National Institutes of
Health.
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Media contact: Melanie Catania, (615) 322-NEWS
melanie.moran@vanderbilt.edu