Exercise-induced Neurogenesis: How Skeletal Muscle Generates New Neurons in the Brain

Neurogenesis in the brain occurs from exercise.

Neurogenesis is the generation of new neurons in the brain. Exercise facilitates this process through a signal protein called VEGF.

It was once thought that neurons in the brain are unable to re-generate. While this is largely true, neurons can regenerate through a process called neurogenesis. In many parts of the body, when a tissue is injured the body is able to easily repair itself. The skin, for example, is constantly subjected to injury, but is able to easily regenerate new skin cells to replace the dying skin cells. Another example is in the liver. The liver has a remarkable ability to regrow itself after injury. The brain, however, is not so fortunate. This is why patients have such a difficult road to rehabilitation after an insult to the brain such as a stroke. After a stroke, most of the neurons, or the workhorse cells of the brain, will not return. In some areas, the adult brain continues to display an ability to generate new neurons, a process called neurogenesis. One area is the hippocampus, which serves as the memory center of the brain. The hippocampus is usually protected during whole brain radiation therapy because of its important effect on memory. Studies have confirmed the ability of the adult humanbrain to produce new neurons through neurogenesis. These studies used radioactive dating based on isotopes present in the atmosphere following detonation of nuclear bombs to date when neurons were generated.

Studies in mice have demonstrated the role of exercise in neurogenesis. Exercising mice, for example, have been shown to perform better at cognitive and memory-oriented tasks such as the water maze. It was subsequently found that neurogenesis in the hippocampus relied on a signaling protein called VEGF (vascular endothelial growth factor).

VEGF, as the name suggests, is involved in the production of new blood vessels. VEGF is important for skeletal muscle to produce new blood vessels, a process called angiogenesis. In endurance athletes, VEGF is produced in response to muscle hypoxia, or low oxygen, for new blood vessels to be developed. VEGF is produced in several places including by skeletal muscles and the heart. VEGF is also important signalling mechanism in several pathologies including cancer and macular degeneration. Avastin (bevacizumab) is drug used in many kinds of cancer and macular degeneration to prevent vascular proliferation by inhibiting VEGF.

Research found that when VEGF was blocked from crossing the blood brain barrier, neurogenesis was halted in response to exercise. The next question was where the source of VEGF was coming from. This was answered in a study that knocked out VEGF production in the skeletal mucle of exercising mice (Skeletal myofiber vascular endothelial growth factor is require for the exercise training-induced increase in dentate gyrus neuonal precursor cells, 2017. Rich B, et al). It was found that both neurogenesis and cerebral blood flow in the hippocampus was reduced in the exercising mice without VEGF expression in exercising mice.

This demonstrates the connection between our skeletal muscle, brain blood flow and neurogenesis in the hippocampus. That connection appears to be VEGF produced in the skeletal muscle.

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