How does the skeletal muscle communicate with the brain in health and disease?

• Published in: Neuropharmacology Vol. 197; p. 108744
• Main Authors: Isaac, Alinny R., Lima-Filho, Ricardo A.S., Lourenco, Mychael V.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2021
• Subjects: Alzheimer's disease; Animals; Brain - metabolism; Brain - physiology; Brain Chemistry - physiology; Cognition; Depression; Hormones; Humans; Mood; Muscle, Skeletal - innervation; Muscle, Skeletal - physiology; Myokines; Neurodegeneration; Physical exercise; Signal Transduction - physiology; Skeletal muscle; Myokines; Physical exercise; Mood; Neurodegeneration; Depression; Cognition; Hormones; Alzheimer's disease; Skeletal muscle
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2021.108744

Endocrine mechanisms have been largely associated with metabolic control and tissue cross talk in mammals. Classically, myokines comprise a class of signaling proteins released in the bloodstream by the skeletal muscle, which mediate physiological and metabolic responses in several tissues, including the brain. Recent exciting evidence suggests that myokines (e.g. cathepsin B, FNDC5/irisin, interleukin-6) act to control brain functions, including learning, memory, and mood, and may mediate the beneficial actions of physical exercise in the brain. However, the intricate mechanisms connecting peripherally released molecules to brain function are not fully understood. Accumulating findings further indicates that impaired skeletal muscle homeostasis impacts brain metabolism and physiology. Here we review recent findings that suggest that muscle-borne signals are essential for brain physiology and discuss perspectives on how these signals vary in response to exercise or muscle diseases. Understanding the complex interactions between skeletal muscle and brain may result in more effective therapeutic strategies to expand healthspan and to prevent brain disease. This article is part of the special Issue on ‘Cross Talk between Periphery and the Brain’. •Muscle-derived molecules play key roles in cognition and mood.•Myokines trigger signaling mechanisms that favor synapse plasticity in the brain.•Metabolic disorders and skeletal muscle disease may impair brain function.•Physical exercise may boost muscle-brain communication, cognition and mood.