How
physical exercise protects the brain from stress-induced 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.
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.
Story Source:
The above story is based on materials provided by Karolinska Institutet. Note: Materials may be edited for
content and length.
Journal Reference:
Leandro Z. Agudelo, Teresa FemenÃa, Funda Orhan,
Margareta Porsmyr-Palmertz, Michel Goiny, Vicente Martinez-Redondo, Jorge C.
Correia, Manizheh Izadi, Maria Bhat, Ina Schuppe-Koistinen, Amanda Pettersson,
Duarte M. S. Ferreira, Anna Krook, Romain Barres, Juleen R. Zierath, Sophie
Erhardt, Maria Lindskog, and Jorge L. Ruas. Skeletal
Muscle PGC-1a1 Modulates Kynurenine Metabolism and Mediates Resilience to
Stress-Induced Depression. Cell,
September 2014
Cite This Page:
Karolinska Institutet. "How physical exercise
protects the brain from stress-induced depression." Science Daily,
25 September 2014.
<www.sciencedaily.com/releases/2014/09/140925131345.htm>.