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Friday, August 28, 2015
Parkinson’s Disease Brain Cells at Risk of Burnout, Like an Overheating Motor
find that the brain cells most at risk in the disease consume unusually high
amounts of energy, gradually exhausting and killing themselves.
August 28, 2015 — The death of brain cells in Parkinson’s disease may be caused
by a form of cellular energy crisis in neurons that require unusually high
quantities of energy to carry out their job of regulating movement, researchers
at the University of Montreal reported today.
The neurodegenerative disorder
affects over 100,000 Canadians and over 1,000,000 Americans.
“Like a motor
constantly running at high speed, these neurons need to produce an incredible
amount of energy to function. They appear to exhaust themselves and die
prematurely,” said lead researcher Louis-Éric Trudeau, a professor at the
university’s Departments of Phamacology and Neurosciences.
article, published today in Current Biology, includes contributions from
Consiglia Pacelli, Nicolas Giguère and Marie-Josée Bourque, also of the
University of Montreal, and Martin Lévesque and Ruth Slack, of Laval and Ottawa
findings are in some ways a culmination of Trudeau’s 17 years of studying the
part of the brain that causes Parkinson’s disease, schizophrenia and drug
addiction. His findings could open the door to the creation of better animal
models of Parkinson’s disease and the identification of new treatment
“For some unknown reason, it has been incredibly difficult to
reproduce the symptoms of Parkinson’s in mice, even when introducing in the
genome of these animals the same mutations found in humans afflicted by
familial forms of the disease. Our discovery provides a new lead to potentially
overcome such difficulties” Trudeau explained.
animal models open a variety of new avenues of research. “It’s possible that
new medications could be developed to help the neurons in question reduce their
energy consumption or produce energy more efficiently, which would reduce
accumulated damage over the years,” Trudeau said.
His team is already looking
at the possible next steps with Professor Slack and her colleague Professor
the dark side
Unlike Alzheimer’s, which has a wider-ranging impact on billions of brain
neurons, the primary symptoms or Parkinson’s are caused by the death of tens or
hundreds of thousands of neurons in a few more restricted areas of the brain,
including regions called the substantia nigra (literally “the black
substance”), the locus ceruleus and the dorsal nucleus of the vagus nerve.
to the mystery may be mitochondria, the powerhouses that allow cells to grow
and neurons to conduct electrical signals and release their chemical messengers
such as dopamine, noradrenaline and acetylcholine. For the past three years,
the research team carried out numerous experiments in order to identify why
mitochondria in neurons of the substantia nigra work so hard and apparently
lead neurons to “overheat”.
discovered that this overheating could be caused by the fact that these neurons
have an amazingly complex structure with a large number of extensions and
neurotransmitter release sites, much like a tree with numerous branches.
energy to these numerous branches may make the neurons particularly vulnerable,
leading, in the context of aging, to malfunction and cell death, thus
triggering Parkinson’s, with the onset of symptoms generally at around age
“Our work supports the theory that very complex neurons like those found
in the substantia nigra force the mitochondria to constantly work at burnout
rates to produce energy. This would explain the accelerated cell
deterioration,” Trudeau explained.
“To use the analogy of a motor, a car that
overheats will burn significantly more fuel, and, not surprisingly, end up at
the garage more often.”
Trudeau notes that the most common neurodegenerative diseases are particularly
challenging for researchers, because in a way, their increasing prevalence is
the result of increased life expectancy.
“From an evolutionary standpoint, some
of our neurons are perhaps just not programmed to last 80, 90 or 100 years, as
we are seeing more and more. It’s to be expected that certain parts of our body
are less able to withstand the effects of time,” he said.
However, given the
more localized nature of Parkinson’s disease (compared to other afflictions),
an effective treatment may be discovered in the not-too-distant future.
Nevertheless, Trudeau points out that his primary goal is to develop a
fundamental understanding of the mechanisms of the brain in order to shed new
light on neurological disorders.
Professor Louis-Éric Trudeau and his team are affiliated with the University of
Montreal’s Groupe de Recherche sur le Système Nerveux Central, Department of
Pharmacology and Department of Neurosciences. Trudeau and his colleagues
published “"Elevated mitochondrial bioenergetics and axonal arborization
size are key contributors to the vulnerability of dopamine neurons" inCurrent
Biology on August 27, 2015.
research team received support for this project from Brain Canada in
partnership with the Krembil Foundation, as well as from Parkinson Society
University of Montreal is officially known as Université de Montréal.