Do Our Muscles and Brain Talk to Each Other?

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Have you ever experienced a runner’s high or an instant mood boost from finishing a workout? If so, you can thank endorphins which are chemicals in the brain that are the body’s natural mood elevators and painkillers. Exercise stimulates the production of endorphins which reduces levels of the body’s stress hormones such as adrenaline and cortisol. Not only can exercise be used as a natural stress reliever and mood booster, but some recent findings also suggest that physical activity has a direct impact on cognitive function. Bente Klarlund Pederson from the Centre of Inflammation and Metabolism (CIM) and Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen discusses how humans developed from apes to Homo sapiens when they began to walk on two feet. Early hominins underwent massive development of skeletal muscle and major changes in their brain capacity in parallel. This is suggesting that humans are not only reliant on exercise for muscle growth and physical performance, but it is actually essential to activating and increasing the number of neuronal connections for optimum cognitive functioning. Since today’s humans are not dependent on a successful hunt and gather for sustenance, the integration of exercise into our daily lives is often lacking or completely lost. This type of physically inactive lifestyle has proven to be detrimental to not only our physical health with increased risk of obesity, diabetes and heart disease, but our mental health as well.

“Regular exercise can lower the rate of cognitive decline in patients with neurodegenerative disorders and in healthy people of all ages, and seems to have a positive influence on stress, anxiety and depression.”

Historical and evolutionary evidence suggests a strong link between physical activity and cognitive functioning. From a scientific perspective, evidence is also now accumulating that moderate-to-vigorous physical activity has many beneficial effects on brain health and cognitive function. Physical activity decreases the risk of diseases such as dementia and might also be useful in the treatment of this disease. Regular exercise can lower the rate of cognitive decline in patients with neurodegenerative disorders and in healthy people of all ages and seems to have a positive influence on stress, anxiety and depression. More specifically, exercise increases muscular expression of kynurenine aminotransferases, which convert blood levels of neurotoxic kynurenine (a microbial metabolite of the essential amino acid tryptophan) to the neuroprotective kynurenic acid, thereby reducing depression-like symptoms. One study found that cognitive decline is almost twice as common among inactive adults versus those who live an active lifestyle. Physical exercise has also been shown to have positive effects on learning, memory and attention, processing speed and executive functions, reaction time and language learning, motor skills and learning, verbal and visuospatial cognitive test results, and academic achievement in children and intelligence in adolescents. Benefits of exercise on cognitive function have largely been shown to be related to aerobic exercise; more research is needed on the possible effects of resistance training.

“… research has shown that exercise reduces dementia risk by increasing blood flow to the brain, reducing inflammation, reducing stress, improving sleep and helping maintain a healthy body weight.”

A review of the literature concluded that a large network of brain areas, equal to 82% of the total gray matter volume, was modifiable by physical activity. The brain region most affected by exercise is the hippocampus which is involved in memory and learning. More specifically, exercise is shown to increase the volume and rate of neuronal formation in the hippocampus, firing more electrical signals for optimum brain function, thereby protecting memory and learning. Considering hippocampal atrophy is the hallmark of Alzheimer’s disease, supporting hippocampal plasticity, which exercise has been shown to do, is incredibly important in reducing the risk of neurodegenerative symptoms. Prior research has shown that exercise reduces dementia risk by increasing blood flow to the brain, increasing neurogenesis (the growth of new nerve cells), reducing inflammation, reducing stress, improving sleep and helping maintain a healthy body weight. Understanding exactly how exercise impacts the size and function of this brain region could even allow researchers to reverse engineer treatments for cognitive conditions such as dementia.

“Current findings suggest the existence of a muscle–brain endocrine loop.”

Until recently, the understanding of how exercise is sensed by the brain was limited. Current findings suggest the existence of a muscle–brain endocrine loop. Working skeletal muscle secretes molecules called myokines, or expresses muscle factors that can alter hippocampal function either directly or via an effect on levels of the nerve growth factor BDNF. Evidence is accumulating that the myokine cathepsin B, when increased peripherally by exercise, can pass through the blood–brain barrier and enhance BDNF production and hence neurogenesis, memory and learning. Moreover, the PGC1α-dependent myokine irisin, which is released into the circulation by cleavage of FNDC5, might reach the brain and activate the FNDC5–BDNF pathway. Direct muscle-to-brain crosstalk is mediated by myokines and metabolites released by muscle, but exercise is also sensed by the brain indirectly via adipose tissue and the liver. These organs secrete other groups of signaling molecules called adipokines and hepatokines, which can pass through the blood–brain barrier and affect brain regions.

“The connection between exercise and brain function has the potential to highlight novel therapeutic targets for neurodegenerative diseases and cognitive stimulators for all ages.”

The emerging connection between exercise and brain function has the potential to highlight novel therapeutic targets for neurodegenerative diseases and cognitive stimulators for all ages. As the rates of mental illness continue to rise in the US and other developed countries, it is now more urgent than ever to find effective treatment methods and preventative care. Using physical activity as a non-pharmacological treatment offers a widely accessible alternative to medication for those currently suffering or those who are at risk of developing a mental disorder. Although more research is needed before recommending specific treatment plans, there is strong evidence to support physical activity to be highly beneficial for both physical and mental health.

Juliette Frank Juliette Frank is a recent UCLA graduate with a degree in Public Affairs and Food Studies. Her interests include the interrelation between food systems, digestive health, and the environmental impacts of food production.

This article was reviewed and approved by Emeran Mayer, MD