ArticleProceedings of the National Academy of Sciences of the United States of America2024
Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026Review
- Skeletal muscle‑derived extracellular vesicles in multi‑organ degenerative disease: Mechanisms and therapeutic delivery perspectives (Review).International journal of molecular medicine · 2026Review
- Relationship between muscle FNDC5, FGF21 mRNA, miR-150 and bone loss after sciatic denervation.Journal of physiology and biochemistry · 2026Article
- Dynamic integration of skeletal muscle signals via extracellular vesicles in motor neuron diseases.Acta neuropathologica communications · 2026Review
- Shear-Induced CROSS (Cellular RedOx Spreading Shield) Assembly Sustains Neurotrophic Extracellular Vesicle Production for Functional Neural Networks.Advanced functional materials · 2026Article
- Acutely denervated muscle EVs reshape neuronal mitochondrial metabolism via retrograde signaling to rescue peripheral nerve injury.Cell reports. Medicine · 2026Article
- Exercise-specific post-translational modification signatures: unveiling precise regulatory mechanisms of molecular exercise language and cellular adaptation.Frontiers in sports and active living · 2026Review
- Exercise-conditioned extracellular vesicles in Alzheimer's disease: a multi-organ signaling network linking peripheral adaptation to brain pathology.Frontiers in immunology · 2026Review
- Underexplored terrain: effects of high priority environmental toxicants on skeletal muscle.Journal of toxicology and environmental health. Part B, Critical reviews · 2026Review
- 80 years of extracellular vesicles: from discovery to clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Inter-Organ Crosstalk and Regulatory Mechanisms of Skeletal Muscle-Derived Extracellular Vesicles in Systemic Metabolic Homeostasis.Journal of cellular and molecular medicine · 2025Review
- Plasma-Derived Extracellular Vesicle Proteomics.Journal of proteome research · 2025Review
- Optogenetic neuromuscular actuation of a miniature electronic biohybrid robot.Science robotics · 2025Article
- Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review).International journal of molecular medicine · 2025Review
- A forward-engineered, muscle-driven soft robotic swimmer.Science advances · 2025Article
- Leveraging microtopography to pattern multi-oriented muscle actuators.Biomaterials science · 2025Article
- Human iPSC-Derived Motor Neuron Innervation Enhances the Differentiation of Muscle Bundles Engineered with Benchtop Fabrication Techniques.ACS biomaterials science & engineering · 2025Article
- Actuating Extracellular Matrices Decouple the Mechanical and Biochemical Effects of Muscle Contraction on Motor Neurons.Advanced healthcare materials · 2025Article
- Causal association of sarcopenia-related traits with brain cortical structure: a bidirectional Mendelian randomization study.Aging clinical and experimental research · 2025Article
- The protein cargo of extracellular vesicles correlates with the epigenetic aging clock of exercise sensitive DNAmFitAge.Biogerontology · 2025Article
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Authors and funding
25 authors.
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Abstract
Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.
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