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BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle

Delezie, Julien and Weihrauch, Martin and Maier, Geraldine and Tejero, Rocío and Ham, Daniel J. and Gill, Jonathan F. and Karrer-Cardel, Bettina and Rüegg, Markus A. and Tabares, Lucía and Handschin, Christoph. (2019) BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle. Proceedings of the National Academy of Sciences of the United States of America, 116 (32). pp. 16111-16120.

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Official URL: https://edoc.unibas.ch/71475/

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
UniBasel Contributors:Handschin, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
ISSN:0027-8424
e-ISSN:1091-6490
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Language:English
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Last Modified:03 Sep 2019 13:20
Deposited On:03 Sep 2019 13:15

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