Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease

Author(s):Show less -

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

• Document type: Journal article
• Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 113, n. 3, p. 5-pg., 2016-01-19.

Abstract

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)

• FAPESP's process: 12/24524-6 - Control of muscle mass by cAMP signaling pathway
• Grantee: Isis Do Carmo Kettelhut
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/11083-6 - ROLE OF EPAC IN CONTROL OF PROTEIN METABOLISM IN SKELETAL MUSCLE
• Grantee: Wilian de Assis Silveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/05697-7 - Functional interaction between cholinergic and adrenergic systems in the maintenance of muscle mass and motor endplate
• Grantee: Danilo Lustrino Borges
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 12/51456-1 - Role and mechanism of action of anabolic stimuli on neuromuscular trophicity
• Grantee: Isis Do Carmo Kettelhut
• Support Opportunities: Regular Research Grants