Research Blog

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 thehippocampus 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.

Face Masks: The Effect on Exercise Physiology

Woman running with face mask





How does wearing a facemask affect exercise physiology? Several studies find differences in physiological differences when wearing a facemask, but do they actually matter?




For most of us, the COVID-19 pandemic has drastically changed how we exercise. Group exercise activities have been cut. In many places, indoor gyms remain closed and for those that are open often face masks are required. Outdoor physical activity can limit COVID-19 transmission. Nonetheless, some people are more comfortable exercising outdoors with a face mask. What affect does wearing a face mask have on exercise physiology?

A recently published study published in the Scandavian Journal of Medicine and Science in Sports attempts to bring some clarity to this question (Return to training in the COVID-19 era: The physiological effects of face masks during exercise, 2020. Epstein, et al.). This study looked at the physiological effects of wearing a surgical mask or N95 respirator during short, aerobic exercise.

Its important to remember that aerobic exercise involves cardiovascular-type workouts such as running, cycling or walking. In contrast, anaerobic exercise includes weight lifting and sprinting and may have different interaction with wearing a face mask. Aerobic exercise usually puts more stress on the pulmonary system, involving the lungs. Because facemasks principle affect on exercise is breathing (after all they are designed to filter air as we inhale and exhale) it makes to test them in the setting of aerobic exercise.

For the aforementioned study, 16 male volunteers were tested while performing cycling with no mask, a surgical mask and a N-95 respirator. Different physiological parameters were measured such as heart rate, blood pressure, oxygen saturation, time to exhaustion and end-tidal carbon dioxide. The load varied as participants cycled. Participants rated the percieved exertion during the cycling exercise. Patients were randomly assigned to different orders of no mask, surgical mask and N-95 respirator with at least 24 hours of rest between tests.

The participants were able to cycle 18 to 19 minutes until exhaustion with each of the three different tests (N-95, no mask, surgical mask). There was no difference in the time to exhaustion between groups. The authors also reported that there was no difference in the participants physiological parameters such as blood pressure, heart rate, respiratory rate, oxygen saturation and percieved exertion. However, there were differences in the end-tidal carbon dioxide.

End-tidal carbon dioxide is a measure of carbon dioxide in our breath at the end of the breathing cycle. Recall that breathing serves two primary purposes. Respiration brings oxygen into the blood stream, which serves as fuel for working muscle. In addition, carbon dioxide, a waste product of cellular metabolism, is revoved from the blood stream in the lungs and exhaled. During aerobic exercise the oxygen consumption and carbon dioxide excretion requirement increase. High levels of carbon dioxide are the primary driver of increased respiratory rate in exercising individuals. High carbon dioxide levels in the blood lead to respiratory acidosis, which leads to feeling short of breath, and with elevation can cause headaches, confusion, anxiety and decreased exercise tolerance.

End-tidal carbon dioxide was significanly higher during cycling with an N-95 mask compared to no mask. Just prior to exhaustion, end-tidal carbon dioxide was higher in the N-95 group compared to both the surgical mask group and no mask group. The surgical mask group had higher end-tidal carbon dioxide compared to the no mask group just prior to exhaustion, but all other time points no difference was elucidated.

End-tidal carbon dioxide in cycling subjects wearing N-95 mask, surgical mask and no mask

Other findings that have been associated with mask use include a small increase in body temperature, something not evaluated in this study. It should also be noted that this study used healthy male subjects with average age of 34. Other studies in participants with respiratory disorders, such as chronic obstructive pulmonary disease (COPD) or asthma, found more physiological differences with wearing an N-95 mask. For example, one study found that in participants with COPD, wearing an N-95 mask during a six minute walk was associated with increased heart rate, respiratory rate and end-tidal carbon dioxide (Risks of N95 Face Mask Use in Subjects with COPD, 2020. Kyung, et al.).

What does the results of these studies suggest? If safe to do so, wearing a surgical mask provides less inhibition to respiration compared an N-95. Since end-tidal carbon dioxide can lead to shortness of breath, it would be expected that physical performance would suffer during competition with either a N-95 or surgical mask. However, it is reassuring that the effects on performance would be minimal given that no statistically significant difference in time to exhaustion was found in the discussed study.


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