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

Published on Jul 18, 2019in Proceedings of the National Academy of Sciences of the United States of America 9.58
· DOI :10.1073/pnas.1900544116
Julien Delezie2
Estimated H-index: 2
(University of Basel),
Martin Weihrauch1
Estimated H-index: 1
(University of Basel)
+ 7 AuthorsChristoph Handschin39
Estimated H-index: 39
(University of Basel)
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.
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Published on Sep 1, 2016in Cell Reports 7.82
Ernest Palomer4
Estimated H-index: 4
(CSIC: Spanish National Research Council),
Adrián Martín-Segura2
Estimated H-index: 2
(CSIC: Spanish National Research Council)
+ 5 AuthorsCarlos G. Dotti58
Estimated H-index: 58
(CSIC: Spanish National Research Council)
Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR)-mediated activation of CaMKII. Decreased NMDAR signaling prevents changes associated with activation at specific Bdnf promoters, including displacement of histone deacetylase 4, recruitment o...
Published on Aug 29, 2016in Human Molecular Genetics 4.54
Rocío Tejero4
Estimated H-index: 4
(University of Seville),
Mario Lopez-Manzaneda1
Estimated H-index: 1
(University of Seville)
+ 1 AuthorsLucia Tabares20
Estimated H-index: 20
(University of Seville)
Jared C. Talbot6
Estimated H-index: 6
(OSU: Ohio State University),
Lisa Maves14
Estimated H-index: 14
(Seattle Children's Research Institute)
Skeletal muscle fibers are classified into fiber types, in particular, slow twitch versus fast twitch. Muscle fiber types are generally defined by the particular myosin heavy chain isoforms that they express, but many other components contribute to a fiber's physiological characteristics. Skeletal muscle fiber type can have a profound impact on muscle diseases, including certain muscular dystrophies and sarcopenia, the aging-induced loss of muscle mass and strength. These findings suggest that s...
Published on May 6, 2016in Journal of Biological Chemistry
Pedro Chacón-Fernández2
Estimated H-index: 2
(Cardiff University),
Katharina Säuberli2
Estimated H-index: 2
(Cardiff University)
+ 3 AuthorsYves-Alain Barde67
Estimated H-index: 67
(Cardiff University)
The biosynthesis of endogenous brain-derived neurotrophic factor (BDNF) has thus far been examined in neurons where it is expressed at very low levels, in an activity-dependent fashion. In humans, BDNF has long been known to accumulate in circulating platelets, at levels far higher than in the brain. During the process of blood coagulation, BDNF is released from platelets, which has led to its extensive use as a readily accessible biomarker, under the assumption that serum levels may somehow ref...
Published on Nov 1, 2015in Nature Communications 11.88
Kevin Y. Lee24
Estimated H-index: 24
Manvendra K. Singh22
Estimated H-index: 22
+ 5 AuthorsC Ronaldkahn155
Estimated H-index: 155
(Harvard University)
Skeletal muscle is composed of both slow-twitch oxidative myofibers and fast-twitch glycolytic myofibers that differentially impact muscle metabolism, function and eventually whole-body physiology. Here we show that the mesodermal transcription factor T-box 15 (Tbx15) is highly and specifically expressed in glycolytic myofibers. Ablation of Tbx15 in vivo leads to a decrease in muscle size due to a decrease in the number of glycolytic fibres, associated with a small increase in the number of oxid...
Published on Feb 1, 2015in Cell 36.22
Douglas M. Anderson10
Estimated H-index: 10
(UTSW: University of Texas Southwestern Medical Center),
Kelly M. Anderson5
Estimated H-index: 5
(UTSW: University of Texas Southwestern Medical Center)
+ 8 AuthorsRhonda Bassel-Duby50
Estimated H-index: 50
(UTSW: University of Texas Southwestern Medical Center)
Summary Functional micropeptides can be concealed within RNAs that appear to be noncoding. We discovered a conserved micropeptide, which we named myoregulin (MLN), encoded by a skeletal muscle-specific RNA annotated as a putative long noncoding RNA. MLN shares structural and functional similarity with phospholamban (PLN) and sarcolipin (SLN), which inhibit SERCA, the membrane pump that controls muscle relaxation by regulating Ca 2+ uptake into the sarcoplasmic reticulum (SR). MLN interacts direc...
Published on Jan 1, 2015in Archives of Medical Science 2.38
Siresha Bathina4
Estimated H-index: 4
Undurti N. Das8
Estimated H-index: 8
Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BD...
Published on Oct 15, 2014in Journal of Applied Physiology 3.14
Carlos Bernardo Mantilla34
Estimated H-index: 34
(Mayo Clinic),
Jessica M. Stowe5
Estimated H-index: 5
(Mayo Clinic)
+ 5 AuthorsGary C Sieck36
Estimated H-index: 36
(Mayo Clinic)
Activation of the tropomyosin-related kinase receptor B (TrkB) by brain-derived neurotrophic factor acutely regulates synaptic transmission at adult neuromuscular junctions (NMJs). The role of TrkB kinase activity in the maintenance of NMJ function and structure at diaphragm muscle NMJs was explored using a chemical-genetic approach that permits reversible inactivation of TrkB kinase activity in TrkBF616A mice by 1NMPP1. Inhibiting TrkB kinase activity for 7 days resulted in significant, yet rev...
Published on Aug 11, 2014in Frontiers in Aging Neuroscience 3.63
Marta Gonzalez-Freire11
Estimated H-index: 11
(NIH: National Institutes of Health),
Rafael de Cabo72
Estimated H-index: 72
(NIH: National Institutes of Health)
+ 1 AuthorsLuigi Ferruci142
Estimated H-index: 142
(NIH: National Institutes of Health)
Aging is associated with a progressive loss of muscle mass and strength and a decline in neurophysiological functions. Age-related neuromuscular junction (NMJ) plays a key role in musculoskeletal impairment that occurs with aging. However, whether changes in the NMJ precede or follow the decline of muscle mass and strength remains unresolved. Many factors such as mitochondrial dysfunction, oxidative stress, inflammation, changes in the innervation of muscle fibers and mechanical properties of th...
Published on May 1, 2014in Nature Communications 11.88
Anne-Sophie Arnold4
Estimated H-index: 4
Jonathan F. Gill3
Estimated H-index: 3
+ 5 AuthorsChristoph Handschin39
Estimated H-index: 39
(University of Basel)
The peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α) is implicated in regulating the morphology and function of the neuromuscular junction. Here, Arnold et al. show that PGC-1α promotes the remodeling of pre- and postsynaptic neuromuscular junction sites, even in the absence of physical activity.
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