Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease

Autor(es):Mostrar menos -

Khan, Muzamil Majid ^{[1, 2, 3]} ; Lustrino, Danilo ^{[4, 5]} ; Silveira, Willian A. ^{[4, 5]} ; Wild, Franziska ^{[1, 2, 3]} ; Straka, Tatjana ^{[1, 2, 3]} ; Issop, Yasmin ^[6] ; O'Connor, Emily ^[6] ; Cox, Dan ^[6] ; Reischl, Markus ^[7] ; Marquardt, Till ^[8] ; Labeit, Dittmar ^[9] ; Labeit, Siegfried ^[9] ; Benoit, Evelyne ^{[10, 11]} ; Molgo, Jordi ^{[10, 11]} ; Lochmueller, Hanns ^[6] ; Witzemann, Veit ^[12] ; Kettelhut, Isis C. ^{[4, 5]} ; Navegantes, Luiz C. C. ^{[5, 4]} ; Pozzan, Tullio ^{[13, 14]} ; Rudolf, Ruediger ^{[1, 2, 3]}

Afiliação do(s) autor(es):Mostrar menos -

^[1] Heidelberg Univ, Interdisciplinary Ctr Neurosci, D-69120 Heidelberg - Germany

^[2] Hsch Mannheim, Inst Mol & Cell Biol, D-68163 Mannheim - Germany

^[3] Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76344 Eggenstein Leopoldshafen - Germany

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto - Brazil

^[5] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto - Brazil

^[6] Newcastle Univ, John Walton Muscular Dystrophy Res Ctr, Med Res Council Ctr Neuromuscular Dis, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear - England

^[7] Karlsruhe Inst Technol, Inst Appl Informat, D-76344 Eggenstein Leopoldshafen - Germany

^[8] European Neurosci Inst, Dev Neurobiol Lab, D-37077 Gottingen - Germany

^[9] Heidelberg Univ, Dept Integrat Pathophysiol, D-68167 Mannheim - Germany

^[10] CEA, Inst Biol & Technol Saclay iBiTec S, Serv Ingn Mol Prot SIMOPRO, F-91191 Gif Sur Yvette - France

^[11] Univ Paris 11, CNRS, Inst Neurosci Paris Saclay, UMR 9197, F-91190 Gif Sur Yvette - France

^[12] Max Planck Inst Med Res, D-69120 Heidelberg - Germany

^[13] Univ Padua, Dept Biomed Sci, I-35121 Padua - Italy

^[14] CNR, Inst Neurosci, Padua Sect, I-35121 Padua - Italy

• Tipo de documento: Artigo Científico
• Fonte: Proceedings of the National Academy of Sciences of the United States of America; v. 113, n. 3, p. 746-750, JAN 19 2016.
• Citações Web of Science: 32

Resumo

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 beta 2-adrenoreceptor (ADRB2), cAMP production, and import of the transcriptional coactivator peroxisome proliferator-activated receptor gamma-coactivator 1 alpha (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. (AU)

• Processo FAPESP: 12/24524-6 - Controle da massa muscular pela via de sinalização do AMPc
• Beneficiário: Isis Do Carmo Kettelhut
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/05697-7 - Interação funcional entre o sistema colinérgico e adrenérgico na manutenção da massa muscular e da placa motora
• Beneficiário: Danilo Lustrino Borges
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 10/11083-6 - Papel da epac no controle do metabolismo protéico em músculos esqueléticos
• Beneficiário: Wilian de Assis Silveira
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/51456-1 - Role and mechanism of action of anabolic stimuli on neuromuscular trophicity
• Beneficiário: Isis Do Carmo Kettelhut
• Linha de fomento: Auxílio à Pesquisa - Regular