文章发表在Nature Neuroscience上。
https://www.sciencedaily.com/releases/2010/12/101205202510.htm
ScienceDaily (Dec. 6, 2010) — The season in which babies are born can have a
dramatic and persistent effect on how their biological clocks function.
That is the conclusion of a new study published online on Dec. 5 by the journa
l Nature Neuroscience. The experiment provides the first evidence for seasonal
imprinting of biological clocks in mammals and was conducted by Professor of
Biological Sciences Douglas McMahon, graduate student Chris Ciarleglio, post-d
octoral fellow Karen Gamble and two undergraduate students at Vanderbilt Unive
rsity.
The imprinting effect, which was found in baby mice, may help explain the fact
that people born in winter months have a higher risk of a number of neurologi
cal disorders including seasonal affective disorder (winter depression), bipol
ar depression and schizophrenia.
"Our biological clocks measure the day length and change our behavior accordin
g to the seasons. We were curious to see if light signals could shape the deve
lopment of the biological clock," said McMahon.
In the experiment, groups of mouse pups were raised from birth to weaning in a
rtificial winter or summer light cycles. After they were weaned, they were mai
ntained 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 patt
erns were observed.
The winter-born mice showed a consistent slowing of their daily activity perio
d, 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 t
he master biological clocks in the mouse brains, using a gene that makes the c
lock cells glow green when active, they found a similar pattern: slowing of th
e gene clocks in winter-born mice compared to those born on a summer light cyc
le.
"What is particularly striking about our results is the fact that the imprinti
ng affects both the animal's behavior and the cycling of the neurons in the ma
ster biological clock in their brains," said Ciarleglio.
In addition, their experiments found that the imprinting of clock gene activit
y near birth had dramatic effects on the reaction of the biological clock to c
hanges in season later in life. The biological clocks and behavior of summer-b
orn mice remain stable and aligned with the time of dusk while that of the win
ter-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 sci
entists intend to address in future experiments.
Seasonality and Personality
The new study raises an intriguing but highly speculative possibility: seasona
l variations in the day/night cycle that individuals experience as their brain
s 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 ha
ve a more general effect on personality," said McMahon.
"It's important to emphasize that, even though this sounds a bit like astrolog
y, it is not: it's seasonal biology!" McMahon added.
Mice in this study were raised on artificial seasonal light cycles in the labo
ratory and the study was repeated at different times of the year. In humans, s
tudies conducted in the northern and southern hemispheres have confirmed that
it's the season of winter -- not the birth month -- that leads to increased ri
sk of schizophrenia. There are many possible seasonal signals that could affec
t brain development, including exposure to flu virus. This study shows that se
asonal 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 m
ice that it took McMahon two years to develop. The mice have an extra gene ins
erted in their genome that produces a naturally fluorescent green protein caus
ing the biological clock neurons in their brains to glow green when they are a
ctive. This allows the scientists to directly monitor the activity of the mast
er biological clock, which is located in the middle of the brain behind the ey
es 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/n
ight cycles. One group was placed in a "summer" cycle with 16 hours of light a
nd eight hours of dark; another group was placed in a "winter" cycle with eigh
t hours of light and 16 hours of dark; and a third group was placed in an equi
nox cycle with 12 hours of light and 12 hours of darkness. They were kept in t
hese environments for three weeks until they were weaned.
"When they are born, the brains of mice are less developed than those of a hum
an 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 cy
cle and half were switched to the winter cycle for the following 28 days as th
ey matured. The winter-born mice were given the same treatment. The equinox-bo
rn mice were split into three groups and put into summer, winter and equinox c
ycles.
After the mice matured, they were placed into an environment of continuous dar
kness. This eliminated the day/night cues that normally reset biological clock
s and allowed the scientists to determine their biological clock's intrinsic c
ycles.
The scientists found a substantial difference between the summer-born and wint
er-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 du
sk (as determined by their former day/night cycle), continued for ten hours an
d then rested for 14 hours.
The behavior of the winter-born mice was much different. Those who had been ke
pt on the winter light cycle through maturation showed basically the same patt
ern as their summer cousins: They became active at the time of dusk and contin
ued for 10 hours before resting. However, those who had been switched to a sum
mer 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 mature
d 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 fe
ll midway between the summer and winter groups. Those subjected to a summer cy
cle when they matured had biological clocks that peaked one hour before the ti
me of dusk and the biological clocks of those subjected to a winter cycle peak
ed a half hour after the time of dusk. In both cases the duration of SCN activ
ity was 11 hours.
Their analysis showed that these variations are caused by alterations in the a
ctivity patterns of the individual neurons, rather than by network-level effec
ts.
"It is quite striking how closely the neuronal wave form and period line up wi
th their behavior," McMahon said.
###
Ciarleglio completed his graduate studies and is now assistant director of the
Vanderbilt Brain Institute. The undergraduate contributors to the study were
John Axley and Benjamin Strauss, who have graduated and gone onto graduate sch
ool and medical school. Karen Gamble, the contributing post-doctoral fellow, i
s now a faculty member in the psychiatry department at the University of Alaba
ma Birmingham.
The research was funded by grants from the National Institutes of Health and w
as conducted in association with the Silvio O. Conte Neuroscience Research Cen
ter at Vanderbilt.
Disclaimer: This article is not intended to provide medical advice, diagnosis
or treatment. Views expressed here do not necessarily reflect those of Science
Daily or its staff.
Email or share this story:
| More
Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily s
taff) from materials provided by Vanderbilt University.
Journal Reference:
1. Christopher M Ciarleglio, John C Axley, Benjamin R Strauss, Karen L Gamb
le, Douglas G McMahon. Perinatal photoperiod imprints the circadian clock. Nat
ure Neuroscience, 2010; DOI: 10.1038/nn.2699
