Quebec researchers achieve A major breakthrough in understanding bipolar disorder and depression

    QUEBEC CITY, Feb. 7 /CNW Telbec/ - Since lithium was first used, over
three decades ago, as a first- line treatment for bipolar disorder, also known
as manic-depressive syndrome, its mode of action has been gradually updated.
Dr. Martin J. Beaulieu, who holds a Canada Research Chair at the Centre de
recherche Université Laval Robert-Giffard (CRULRG) in Quebec City, along with
his colleagues from Dr. Marc G. Caron's team at Duke University in Durham,
North Carolina, recently published an article in the prestigious scientific
journal Cell describing a cellular mechanism that could finally explain the
mode of action of lithium on behaviour - a finding that could lead to new
forms of treatment. These results were further affirmed in another discovery,
on the action of serotonin, which was also announced in a paper published by
Dr. Beaulieu and his colleagues at Duke in the U.S. publication Proceedings of
the National Academy of Sciences (PNAS) last January. In the latter paper, the
authors describe the mechanisms of action common to lithium and serotonin, a
neurotransmitter modulated by antidepressant agents.
    "Dr. Beaulieu's achievement is truly a major breakthrough," pointed out
Dr. Michel Maziade, scientific director at the CRULRG and Head of NeuroCité.
"The new technology developed will result in new ways to treat this illness,
which affects 1% of people in Quebec and Canada. We are also very proud to see
this renowned young Québécois researcher come back from the United States to
advance current research on neurons, the brain and brain diseases."
    "As a member of the CRULRG and NeuroCité teams, Dr. Beaulieu will now
enjoy access to an elite researcher network as well as to a unique group of
partnerships and associations between private entreprise, the academic world
and the scientific community," continued Dr. Maziade.

    The discovery

    Following their activation by dopamine D2 dopaminergic receptors initiate
cascades of cellular signaling events leading to physiological neuronal
responses. Among these, D2 receptors induce the formation of a signaling
complex of composed kinases and phosphatases held together by a protein termed
beta-arrestin 2. In a previous study, the scientists have shown that lithium
affects the behavior of genetically modified mice by interfering with D2
receptor signaling functions. The behaviors of these genetically modified mice
is reminiscent of those of individuals treated with amphetamine, a drug used
to model psychotic and maniac behaviors in humans.
    Using mice in which the gene encoding beta-arrestin 2 has been
inactivated, the scientists observed that many of the behaviors associated
with D2 receptor activation were dependent upon beta-arrestin 2 "We have then
examined whether the effects of lithium involved the kinase- phosphatase
complex that is held together by beta-arrestin 2," said Dr. Beaulieu. "We
observed that lithium selectively destabilizes this complex."
    "Although this mechanism may not explain all of lithium's therapeutic
effects, this discovery can represent an important step toward the development
of new drugs with similar mechanism of action but without many of the
undesirable side effects of lithium."
    In addition to his Canada Research Chair, Dr. Beaulieu has been awarded
grants by the Canada Institutes of Health Research (CIHR) and the National
Alliance for Research on Schizophrenia and Depression (NARSAD).

    About the Centre de recherche Université Laval Robert-Giffard

    The CRULRG's mission is to accelerate the development of science and
technology related to the neuron, the brain and brain diseases. Over the past
five years, the activities pursued by the Centre have more than doubled, with
$10M in annual scientific grants obtained from both national and international
sources. The CRULRG team is comprised of 400 researchers, Masters and
Doctoral-level students in training, and highly qualified personnel.

    About NeuroCité

    NeuroCité is a world-class private, industrial and academic complex that
interacts with the Centre de recherche Université Laval Robert-Giffard. Its
objective is to increase society's return on investment in science and its
applications, by reducing development time for new technologies in order to
bring them to market more quickly. NeuroCité acts as a catalyst for scientific
activity that is already well established in the Estimauville area of Quebec

For further information:

For further information: Muriel Haraoui, Consultant, HKDP Communications
and public affairs, (514) 395-0375, extension 235, Cellular: (514) 717-3764,; Source: La NeuroCité

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