Just when is your doctor going to condescend to talk to the hospital nutritionist to get a stroke diet protocol set up? NEVER?
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Glutamate is an amino acid with very different functions: in the
pancreas, it modulates the activity of the pancreatic ß-cells
responsible for insulin production, whereas in the brain it is the main
excitatory neurotransmitter. In recent years, it has been suspected to
play an additional role in the functioning of the brain. By discovering
how the brain uses glutamate to produce energy, researchers at the
University of Geneva (UNIGE) confirm this hypothesis and highlight
unexpected links with the rest of the body. To read in Cell Reports.
Unlike other organs, the brain cannot draw its energy from lipids, an
energy resource widely present in the body. The blood-brain barrier,
which protects it from the pathogens and toxins circulating in the
blood, indeed limits the passage of these lipids. Moreover, while most
of the organs in the human body have the ability to store glucose by
increasing their mass, the brain, prisoner of the cranial bones, cannot
count on these variations in volume. Unable to store its food, it
depends on sugar supplied in real-time by the rest of the body. This
distribution of energy is controlled by the liver.
Pierre Maechler, professor at the Faculty of Medicine at UNIGE, and
his team therefore decided to verify if glutamate was indeed an energy
source for the brain. To do so, the researchers analyzed the role of the
glutamate dehydrogenase enzyme in the brain. In mutant form, this
enzyme, encoded by the Glud1 gene, is responsible for a congenital
hyperinsulinism syndrome, a severe disease affecting at the same time
the endocrine pancreas, the liver and the brain. Individuals affected by
this syndrome suffer from intellectual disability and have a high risk
of epilepsy. "We have suppressed the Glud1 gene in the brain of mice. In
the absence of glutamate dehydrogenase, we observed that the brain was
no longer able to convert glutamate into energy, even though the amino
acid was present in the brain," explains Melis Karaca, first author of
this study.
Priority to the brain
Devoid of the energy supplied by cerebral glutamate, the brain sends
signals to the liver to requisition a compensatory proportion of
glucose, at the expense of the rest of the body. This is why the
transgenic mice also showed a growth deficit and muscle atrophy. "This
clearly shows how the brain works in a just-in-time manner and that each
percent of energy resources is essential for its proper functioning,"
highlights Professor Pierre Maechler. "If a part of this energy
disappears, the brain serves itself first and the rest of the body
suffers. The liver must then make more glucose by drawing upon muscle
protein, resulting in loss of muscle mass. Knowing that the brain uses
glutamate as an energy resource allows us to reflect on other ways to
overcome a potential shortfall. "
Scientists also suspect a correlation between the Glud1 gene and some
neurodevelopmental disorders, particularly epilepsy and schizophrenia.
They are currently pursuing their research by introducing in mice the
same Glud1 mutation detected in epileptic patients. At the same time,
another group is working with schizophrenic patients to assess the way
their brain uses glutamate.
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