BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle
BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle
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DOI：
10.1073/pnas.1900544116
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发表时间：
2019-08-06
影响因子：
11.1
通讯作者：
Handschin, Christoph
中科院分区：
文献类型：
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作者：
Delezie, Julien;Weihrauch, Martin;Handschin, Christoph
脑源性神经营养因子（BDNF）影响中枢神经元的分化、可塑性和存活，同样影响神经肌肉系统的发育。除了神经元来源外，BDNF也是肌因子家族的成员。然而，骨骼肌源性BDNF在体内调节神经肌肉生理学中的作用仍不清楚。使用获得和丧失功能的动物模型，我们表明，肌肉特异性的BDNF消融将肌纤维的比例从IIB型转移到IIX型，伴随着缓慢肌肉型基因表达的升高。此外，BDNF缺失减少运动终板体积，而不影响神经肌肉接头（NMJ）的完整性。这些形态学变化与缓慢的肌肉功能和对收缩引起的疲劳的更大抵抗力有关。相反，BDNF过表达促进快速肌肉型基因程序并提高糖酵解纤维数量。这些发现表明，BDNF是纤维类型规范所必需的，并提供了其作为肌肉疾病治疗靶点的潜在调节的见解。
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.