Biological clock affected by season of birth
9 Dec 2010
The season in which babies are born can have a dramatic and
persistent effect on how their biological clocks function, according to
a study on baby mice conducted by a team from Vanderbilt University.
The researchers raised mice in artificial winter and summer cycles
and then studied their activity patterns in winter and summer light
cycles. The experiment provides the first evidence for seasonal
imprinting of biological clocks in mammals.
The imprinting effect may help explain the fact that people born in
winter months have a higher risk of a number of neurological
disorders including seasonal affective disorder (winter depression),
bipolar depression and schizophrenia.
“Our biological clocks measure the day length and change our
behavior according to the seasons. We were curious to see if light
signals could shape the development of the biological clock,” said
Douglas McMahon, Professor of Biological Sciences Vanderbilt
University.
In the experiment, groups of mouse pups were raised from birth to
weaning in artificial winter or summer light cycles. After they were
weaned, they were maintained in either the same cycle or the
opposite cycle for 28 days. Once they were mature, the mice were
placed in constant darkness and their activity patterns were
observed.
The winter-born mice showed a consistent slowing of their daily
activity period, regardless of whether they had been maintained on a
winter light cycle, or had been shifted to summer cycle after
weaning. When the scientists examined the master biological clocks
in the mouse brains, using a gene that makes the clock cells glow
green when active, they found a similar pattern: slowing of the gene
clocks in winter-born mice compared to those born on a summer light
cycle.
“What is particularly striking about our results is the fact that
the imprinting affects both the animal’s behaviour and the cycling
of the neurons in the master biological clock in their brains,” said
graduate student Chris Ciarleglio.
In addition, their experiments found that the imprinting of clock
gene activity near birth had dramatic effects on the reaction of the
biological clock to changes in season later in life. The biological
clocks and behavior of summer-born mice remain stable and aligned
with the time of dusk while that of the winter-born mice varied
widely when they were placed in a summer light cycle.
“The mice raised in the winter cycle show an exaggerated response
to a change in season that is strikingly similar to that of human
patients suffering from seasonal affective disorder,” McMahon
commented.
Exactly when the imprinting occurs during the three-week period
leading up to weaning and whether the effect is temporary or
permanent are questions the scientists intend to address in future
experiments.
Seasonality and personality
The new study raises an intriguing but highly speculative
possibility: seasonal variations in the day/night cycle that
individuals experience as their brains are developing may affect
their personality.
“We know that the biological clock regulates mood in humans. If
an imprinting mechanism similar to the one that we found in mice
operates in humans, then it could not only have an effect on a
number of behavioral disorders but also have a more general effect
on personality,” said McMahon.
“It’s important to emphasize that, even though this sounds a bit
like astrology, it is not: it’s seasonal biology!” McMahon added.
Mice in this study were raised on artificial seasonal light
cycles in the laboratory and the study was repeated at different
times of the year. In humans, studies conducted in the northern and
southern hemispheres have confirmed that it’s the season of winter —
not the birth month — that leads to increased risk of schizophrenia.
There are many possible seasonal signals that could affect brain
development, including exposure to flu virus. This study shows that
seasonal light cycles can affect the development of a specific brain
function.
“We know from previous studies that light can affect the
development of other parts of the brain, for example the visual
system. Our work shows that this is also true for the biological
clock,” said Ciarleglio.
Background
The experiment was performed with a special strain of genetically
engineered mice that it took McMahon two years to develop. The mice
have an extra gene inserted in their genome that produces a
naturally fluorescent green protein causing the biological clock
neurons in their brains to glow green when they are active. This
allows the scientists to directly monitor the activity of the master
biological clock, which is located in the middle of the brain behind
the eyes in a small area called the suprachiasmatic nucleus (SCN).
For the study, the researchers took three groups of six to eight
newborn pups each and placed them (and their mothers) in
environments with controlled day/night cycles. One group was placed
in a “summer” cycle with 16 hours of light and eight hours of dark;
another group was placed in a “winter” cycle with eight hours of
light and 16 hours of dark; and a third group was placed in an
equinox cycle with 12 hours of light and 12 hours of darkness. They
were kept in these environments for three weeks until they were
weaned.
“When they are born, the brains of mice are less developed than
those of a human baby. As a result, their brains are still being
wired during this period,” McMahon said.
Once they were weaned, half of the summer-born mice were kept on
the summer cycle and half were switched to the winter cycle for the
following 28 days as they matured. The winter-born mice were given
the same treatment. The equinox-born mice were split into three
groups and put into summer, winter and equinox cycles.
After the mice matured, they were placed into an environment of
continuous darkness. This eliminated the day/night cues that
normally reset biological clocks and allowed the scientists to
determine their biological clock’s intrinsic cycles.
The scientists found a substantial difference between the
summer-born and winter-born groups.
The summer-born mice behaved the same whether they had been kept
on the summer cycle or switched to the winter cycle. They started
running at the time of dusk (as determined by their former day/night
cycle), continued for ten hours and then rested for 14 hours.
The behaviour of the winter-born mice was much different. Those
who had been kept on the winter light cycle through maturation
showed basically the same pattern as their summer cousins: They
became active at the time of dusk and continued for 10 hours before
resting. However, those who had been switched to a summer cycle
remained active for an extra hour and a half.
When they looked at what was happening in the brains of the
different groups, they found a strikingly similar pattern.
In the summer-born mice, the activity of the neurons in the SCN
peaked at the time of dusk and continued for 10 hours. When the
winter-born mice were matured in the winter cycle, their neuronal
activity peaked one hour after the time of dusk and continued for 10
hours. But, in the winter-born mice switched to a summer cycle, the
master bioclock’s activity peaked two hours before the time of dusk
and continued for 12 hours.
When they looked at the equinox group, the scientists found
variations that fell midway between the summer and winter groups.
Those subjected to a summer cycle when they matured had biological
clocks that peaked one hour before the time of dusk and the
biological clocks of those subjected to a winter cycle peaked a half
hour after the time of dusk. In both cases the duration of SCN
activity was 11 hours.
Their analysis showed that these variations are caused by
alterations in the activity patterns of the individual neurons,
rather than by network-level effects.
“It is quite striking how closely the neuronal wave form and
period line up with their behavior,” McMahon said.
The study was published online on 5 Dec in the journal Nature
Neuroscience.