BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle
| Autor: | Christoph Handschin, Julien Delezie, Martin Weihrauch, Rocío Tejero, Geraldine Maier, Lucia Tabares, Markus A. Rüegg, Daniel J. Ham, Bettina Karrer-Cardel, Jonathan F. Gill |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Muscle Fibers Skeletal Biology Models Biological Motor Endplate Neuromuscular junction 03 medical and health sciences 0302 clinical medicine Mediator In vivo Neurotrophic factors Physical Conditioning Animal Myokine Gene expression medicine Animals Glycolysis Gait Mice Knockout Multidisciplinary Brain-Derived Neurotrophic Factor Skeletal muscle Cell biology 030104 developmental biology medicine.anatomical_structure PNAS Plus Gene Expression Regulation nervous system Organ Specificity Muscle Fatigue Oxidation-Reduction Locomotion 030217 neurology & neurosurgery Muscle Contraction Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 116:16111-16120 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1900544116 |
| Popis: | Brain-derived neurotrophic factor (BDNF) influences the differentiation, plasticity, and survival of central neurons and likewise, affects the development of the neuromuscular system. Besides its neuronal origin, BDNF is also a member of the myokine family. However, the role of skeletal muscle-derived BDNF in regulating neuromuscular physiology in vivo remains unclear. Using gain- and loss-of-function animal models, we show that muscle-specific ablation of BDNF shifts the proportion of muscle fibers from type IIB to IIX, concomitant with elevated slow muscle-type gene expression. Furthermore, BDNF deletion reduces motor end plate volume without affecting neuromuscular junction (NMJ) integrity. These morphological changes are associated with slow muscle function and a greater resistance to contraction-induced fatigue. Conversely, BDNF overexpression promotes a fast muscle-type gene program and elevates glycolytic fiber number. These findings indicate that BDNF is required for fiber-type specification and provide insights into its potential modulation as a therapeutic target in muscle diseases. |
| Databáze: | OpenAIRE |
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