International Business Department           Liu Bojia           May 14, 2023

  It is well known that regular physical activity strengthens the body and helps to achieve muscle building and fat loss. In addition to the benefits to muscle, cardiovascular and metabolic function, a growing body of research evidence also suggests that exercise can promote brain health. For example, researchers at Harvard Medical School and Massachusetts General Hospital have found that exercise stimulates muscles to secrete a hormone called irisin, which boosts cognitive function in the brain, and is helpful in reducing cognitive decline caused by aging or Alzheimer's disease (AD).

  The molecules released from skeletal muscle are not only hormones such as irisin, but also many small fragments of RNA (i.e., microRNAs) packaged in the form of vesicles (known as "exosomes"). It has been found that these molecules, which enter the bloodstream and then the brain, enhance connections between nerve cells, promote nerve cell function and signalling, and maintain brain homeostasis.

  Since skeletal muscle movement is controlled by the brain and innervated by motor nerves, how muscles release these neurotrophic factors may also be influenced by the stimulation of muscles by motor nerves. In a new study recently published in the Proceedings of the National Academy of Sciences (PNAS), researchers at the University of Illinois at Urbana-Champaign have experimentally confirmed that when motor neurons stimulate muscle movement, it prompts the muscles to secrete a greater number and molecular composition of neurotrophic factors, which is more beneficial to brain health.

  The researchers designed two models of skeletal muscle tissue, one innervated by motor neurons and the other without innervation. The comparison showed that when the neurons of the former were activated, some genes in the muscles they innervated became more active, and these genes were mostly associated with the regulation of secretion. Accordingly, these muscles secreted more irisin and also released more exosomal vesicles.

  Further analysing the material in the vesicles, the researchers found that they also contained a greater diversity of RNA molecules encoding a variety of trophic factors that affect neural development, including the brain-derived neurotrophic factor BDNF, the precursor protein of irisin, FDNC5, and a key regulator of muscle metabolism, PGC-1α.

  Experiments with in vitro cultured neurons have shown that muscle secretion of these bioactive factors enhances branching, axonal transport, and ultimately spontaneous network activity in hippocampal neurons.

  These results further emphasise the "two-way street" between brain and muscle: the brain sends out instructions for nerves to stimulate muscles; in turn, muscles secrete molecules that benefit brain function.

  At the same time, the brain-muscle interplay emphasises the importance of exercise. "Exercise allows for a more robust and robust interactive interface between motor neurons and skeletal muscles." Professor Hyunjoon Kong, lead author of the paper, noted, "We now know that nerves sending signals to muscles cause them to secrete molecules and extracellular vesicles that are beneficial to the brain. Thus, the benefits of exercise are no longer simply increasing muscle size or strength, but can facilitate this muscle-brain connection."