A recent study published in the prestigious journal Cell Jorge Ruas and Maria Lindskog dwells on how physical exercise protects the brain from stress induce depression mice.
We have always known that physical exercise has many beneficial effects on the human health which includes protection of the brain from stress induced depression. However, what were not known till now are the mechanisms that mediate this protective effect. Researchers at the Karolinska Institutet in Sweden show that exercise training induces changes in the skeletal muscles that cleans the blood of a substance that gets accumulated during stress and has harmful effects on the brain.
Depression is a commonly prevalent psychiatric disorder worldwide. According to The World Health Organization (WHO) more than 350 million people suffer from depression.
Mia Lindskog, researcher at the Department of Neuroscience at Karolinska Institutet said that they are still now aware what depression is in neuro biological terms. The study actually represents another piece in the puzzle as the recent study provides an explanation for the protective biochemical changes that occur in the body as a result of exercise. This prevents the brain from getting hampered during stress.
A protein named PGC-1?1 (pronounced PGC-1alpha1) is known to increase the skeletal muscle when one exercises and it paves way for beneficial muscle conditioning in connection with physical activity. For this study, the researchers used a genetically modified mouse that has high levels of PGC-1?1 in skeletal muscle and showed many characteristics of well-trained muscles, even without exercising.
Normal mice and genetically modified mice both were subjected to stressful environment like loud noises, reversed circadian rhythm and flashing lights at irregular intervals. After five weeks of being subjected to stressful environment, the normal mice developed depressive behavior. However the genetically modified mice – those having with well-trained muscle characteristics, showed no depressive symptoms.
Jorge Ruas, principal investigator at the Department of Physiology and Pharmacology, Karolinska Institutet said that their initial hypothesis was that well trained muscles produce a substance that has beneficial effect on the brain. However, the study revealed that well trained muscles produce an enzyme that removes harmful substances from the body. It can be said that the muscle function is like that of kidney or liver.
On further study, researchers found that mice with higher levels of PGC-1?1 in muscle also have higher level of enzymes called KAT. Kats is responsible for converting kyurenine – a substance produced during stress into kynurenic acid a substance that doesn't pass from the blood to the brain. While the exact function of kynurenine is not known, it is seen that high levels of kynurenine is found in patients with mental illness. Researchers also experimented by giving the normal mice doses of kynurenine and they found that these mice showed depressive behavior. However, the genetically modified mice with increased levels of PGC-1?1 in muscle showed no such symptoms. It was observed that the mice with elevated levels of PGC-1?1 never showed increased levels of kynurenine in their blood. That was because the KAT enzymes in their well-trained muscles quickly convert it to kynurenic acid, resulting in a protective mechanism.
Jorge Ruas says that this study is important as it opens up a new pharmacological principle in the treatment of depression, in which attempts could be made to influence skeletal muscle function instead of targeting the brain directly. Skeletal muscle seems to have a detoxification like effect which when activated shows the ability to protect the brain from insults and related mental illness.