EXERCISE CAN PROTECT BRAIN FROM DEPRESSION
Physical exercise has many beneficial effects
on human health, including the protection from stress-induced depression.
However, until now the mechanisms that mediate this protective effect have been
unknown. In a new study in mice, researchers at Karolinska Institutet in Sweden
show that exercise training induces changes in skeletal muscle that can purge
the blood of a substance that accumulates during stress, and is harmful to the
brain. The study is being published in the journal Cell
In neurobiological
terms, we actually still don't know what depression is. Our study represents
another piece in the puzzle, since we provide an explanation for the protective
biochemical changes induced by physical exercise that prevent the brain from being
damaged during stress," says Mia Lindskog, researcher at the Department of
Neuroscience at Karolinska Institutet.
It was known that the
protein PGC-1a1 (pronounced PGC-1alpha1) increases in skeletal muscle with
exercise, and mediates the beneficial muscle conditioning in connection with
physical activity. In this study researchers used a genetically modified mouse
with high levels of PGC-1a1 in skeletal muscle that shows many characteristics
of well-trained muscles (even without exercising).
These mice, and normal
control mice, were exposed to a stressful environment, such as loud noises,
flashing lights and reversed circadian rhythm at irregular intervals. After
five weeks of mild stress, normal mice had developed depressive behaviour,
whereas the genetically modified mice (with well-trained muscle
characteristics) had no depressive symptoms.
"Our initial
research hypothesis was that trained muscle would produce a substance with
beneficial effects on the brain. We actually found the opposite: well-trained
muscle produces an enzyme that purges the body of harmful substances. So in
this context the muscle's function is reminiscent of that of the kidney or the
liver," says Jorge Ruas, principal investigator at the Department of
Physiology and Pharmacology, Karolinska Institutet.
The researchers
discovered that mice with higher levels of PGC-1a1 in muscle also had higher
levels of enzymes called KAT. KATs convert a substance formed during stress
(kynurenine) into kynurenic acid, a substance that is not able to pass from the
blood to the brain. The exact function of kynurenine is not known, but high
levels of kynurenine can be measured in patients with mental illness. In this
study, the researchers demonstrated that when normal mice were given
kynurenine, they displayed depressive behaviour, while mice with increased
levels of PGC-1a1 in muscle were not affected. In fact, these animals never
show elevated kynurenine levels in their blood since the KAT enzymes in their
well-trained muscles quickly convert it to kynurenic acid, resulting in a
protective mechanism.
"It's possible
that this work opens up a new pharmacological principle in the treatment of
depression, where attempts could be made to influence skeletal muscle function
instead of targeting the brain directly. Skeletal muscle appears to have a
detoxification effect that, when activated, can protect the brain from insults
and related mental illness," says Jorge Ruas.
Depression is a common
psychiatric disorder worldwide. The World Health Organization (WHO) estimates
that more than 350 million people are affected.
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