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Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease

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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 ; Molgo, Jordi ; Lochmueller, Hanns ; Witzemann, Veit ; Kettelhut, Isis C. ; Navegantes, Luiz C. C. ; Pozzan, Tullio ; Rudolf, Ruediger
Número total de Autores: 20
Tipo de documento: Artigo Científico
Fonte: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 113, n. 3, p. 5-pg., 2016-01-19.
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
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 10/11083-6 - Papel da epac no controle do metabolismo protéico em músculos esqueléticos
Beneficiário:Wilian de Assis Silveira
Modalidade de apoio: Bolsas no Brasil - Doutorado
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
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 12/51456-1 - Role and mechanism of action of anabolic stimuli on neuromuscular trophicity
Beneficiário:Isis Do Carmo Kettelhut
Modalidade de apoio: Auxílio à Pesquisa - Regular