交感神经支配在健康和疾病状态下控制神经肌肉接头的稳态。
Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease.
作者信息
Khan Muzamil Majid, Lustrino Danilo, Silveira Willian A, Wild Franziska, Straka Tatjana, Issop Yasmin, O'Connor Emily, Cox Dan, Reischl Markus, Marquardt Till, Labeit Dittmar, Labeit Siegfried, Benoit Evelyne, Molgó Jordi, Lochmüller Hanns, Witzemann Veit, Kettelhut Isis C, Navegantes Luiz C C, Pozzan Tullio, Rudolf Rüdiger
机构信息
Interdisciplinary Center for Neurosciences, Universität Heidelberg, 69120 Heidelberg, Germany; Institute of Molecular and Cell Biology, Hochschule Mannheim, 68163 Mannheim, Germany; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany;
Department of Physiology, Faculdade de Medicina de Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, Brazil; Department of Biochemistry and Immunology, Faculdade de Medicina de Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, Brazil;
出版信息
Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):746-50. doi: 10.1073/pnas.1524272113. Epub 2016 Jan 5.
The distribution and function of sympathetic innervation in skeletal muscle have largely remained elusive. Here we demonstrate that sympathetic neurons make close contact with neuromuscular junctions and form a network in skeletal muscle that may functionally couple different targets including blood vessels, motor neurons, and muscle fibers. Direct stimulation of sympathetic neurons led to activation of muscle postsynaptic β2-adrenoreceptor (ADRB2), cAMP production, and import of the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PPARGC1A) into myonuclei. Electrophysiological and morphological deficits of neuromuscular junctions upon sympathectomy and in myasthenic mice were rescued by sympathicomimetic treatment. In conclusion, this study identifies the neuromuscular junction as a target of the sympathetic nervous system and shows that sympathetic input is crucial for synapse maintenance and function.
骨骼肌中交感神经支配的分布和功能在很大程度上仍然不清楚。在这里，我们证明交感神经元与神经肌肉接头紧密接触，并在骨骼肌中形成一个网络，该网络可能在功能上连接包括血管、运动神经元和肌纤维在内的不同靶点。直接刺激交感神经元会导致肌肉突触后β2 - 肾上腺素能受体（ADRB2）激活、cAMP生成以及转录共激活因子过氧化物酶体增殖物激活受体γ - 共激活因子1α（PPARGC1A）导入肌核。交感神经切除术后以及在肌无力小鼠中神经肌肉接头的电生理和形态学缺陷通过拟交感神经治疗得以挽救。总之，本研究确定神经肌肉接头是交感神经系统的一个靶点，并表明交感神经输入对于突触维持和功能至关重要。
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