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Clocks in
the human brain…
First study to show function of clock genes
in multiple areas of the human brain
May
3, 2011--Twenty-four hour cycles, known as
circadian rhythms, are important for proper
body functions, including for normal brain
function and mental health. Disruptions of
circadian rhythms and sleep-wake cycles have
been observed in patients with Alzheimer’s
disease. A new study by Douglas Institute
researchers unravels a possible basis for
these perturbations.
Until now, the
genes contributing to this timing, known as
clock genes, have only been found to be
active in areas outside the brain, such as
the skin and blood cells. Recent findings
from the Douglas Mental Health University
Institute are the first to show that these
genes function in multiple areas of the
human brain as well, as was shown previously
in animals. These findings, published in
this month’s issue of the Journal
of Biological Rhythms,
have implications for the numerous
individuals with sleep disturbances
including those with Alzheimer’s disease.
“To our knowledge,
this is the first demonstration of circadian
clock genes rhythmic expression in the human
forebrain, or the front part of the brain,”
says senior authorNicolas
Cermakian,
a Douglas researcher and Director of the Laboratory
of Molecular Chronobiology.
“In addition, we showed that these rhythms
are disrupted in the brains of Alzheimer’s
patients."
Shape of certain rhythms and the
synchronization between brain areas were
altered in Alzheimer’s patients
Dr. Cermakian and
his colleagues looked for the presence of
the circadian clock genes, PER1, PER2, and
BMAL1 in the brain tissue of 58 donors; 27
were Alzheimer patients and 31 were
controls. (Brain tissue was obtained from
the Brain
Bank of the Douglas.)
All these clock
genes were detected in three brain areas in
both control and Alzheimer patients. In
addition, there was a significant diurnal
(day/night) expression of these genes in all
three structures of control samples. In
samples from Alzheimer’s patients, the shape
of these rhythms and the synchronization
between brain areas were altered.
“The abnormal
clock gene coordination that we observed in
the tissues of Alzheimer’s patients, might
explain the sleep-wake deficits that are
observed in this population,” says Douglas Centre
for Study and Treatment of Circadian Rhythms Director, Diane
B. Boivin.
“The altered sleep pattern worsens with
disease progression and is the most frequent
reason for institutionalization. Improved
understanding of the process that underlies
sleep-wake disruption may lead to better
treatments or therapies. “Our ultimate goal
is to improve the physical and mental health
of individuals by providing scientifically
grounded information.”
Partners in research
The Douglas
Institute Foundation is proud to support
Nicolas Cermakian, PhD and Diane
B. Boivin, MD, PhD,
and their research in mental health. The
Foundation thanks its donors and volunteers
for their generosity and thoughtfulness.
Together, we invest in healthy minds.
This study was
funded by the Canadian Institutes of Health
Research and the Fonds de la recherche en
santé du Québec.
About the study
The article,
“Circadian clock gene expression in brain
regions of Alzheimer’s disease patients and
control subjects", was authored by Nicolas
Cermakian,
Elaine Waddington-Lamont, Philippe Boudreau
and Diane
B. Boivin of
the Douglas Mental Health University
Institute and McGill University.
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