Multiple routes of muscle-to-CNS signaling (IMAGE)
Caption
In response to a variety of stimuli, skeletal muscle can communicate in a number of ways with the central nervous system (CNS), including the following: (1) by secreting signaling proteins (myokines) that can bind to receptors in the blood-brain barrier (BBB) and brain cells (neurons and/or glia), with the consequent induction of downstream signaling; (2) by releasing extracellular vesicles such as exosomes that contain signaling factors; (3) by releasing metabolites (myometabolites) that enter the brain through solute transporters present on the BBB and brain cells; (4) by secreting enzymes that produce signaling factors in the muscle, in the circulation, and/or in the brain; and (5) via indirect effects stemming from modulation of muscle metabolism and/or myokine signaling to other tissues distinct from the brain. Regulated processes include improvement in cerebral blood flow, brain metabolic functions, mitochondrial biogenesis, and neurogenesis, whereas protective signaling reduces oxidative stress, cell senescence, and neuroinflammation. Altogether, the action of muscle-brain signaling on these cellular processes improves cognitive functions.
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Credit: Mamta Rai and Fabio Demontis, Brain Plasticity
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