The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability

<b>Aim:</b> Symptoms of autonomic failure are frequently the presentation of advanced age and neurodegenerative diseases that impair adaptation to common physiologic stressors. The aim of this work was to examine the interaction between the sympathetic and motor nervous system, the invol...

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Autores principales: Zaia Rodrigues, Anna Carolina, Messi, María Laura, Wang, Zhong-Min, Abba, Martín Carlos, Pereyra, Andrea S., Birbrair, Alexander, Zhang, Tan, O’Meara, Meaghan, Kwan, Ping, Silva López, Elsa Idaliz, Willis, Monte S., Mintz, Akiva, Files, D. Clark, Furdui, Cristina M., Oppenheim, Ronald W., Delbono, Osvaldo
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2018
Materias:
Ciencias Médicas
Skeletal muscle
Muscle innervation
Sympathetic nervous system
Muscle denervation
Neuromuscular junction
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/127183
https://onlinelibrary.wiley.com/doi/10.1111/apha.13195
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-127183
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Skeletal muscle
Muscle innervation
Sympathetic nervous system
Muscle denervation
Neuromuscular junction
spellingShingle Ciencias Médicas
Skeletal muscle
Muscle innervation
Sympathetic nervous system
Muscle denervation
Neuromuscular junction
Zaia Rodrigues, Anna Carolina
Messi, María Laura
Wang, Zhong-Min
Abba, Martín Carlos
Pereyra, Andrea S.
Birbrair, Alexander
Zhang, Tan
O’Meara, Meaghan
Kwan, Ping
Silva López, Elsa Idaliz
Willis, Monte S.
Mintz, Akiva
Files, D. Clark
Furdui, Cristina M.
Oppenheim, Ronald W.
Delbono, Osvaldo
The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability
topic_facet Ciencias Médicas
Skeletal muscle
Muscle innervation
Sympathetic nervous system
Muscle denervation
Neuromuscular junction
description <b>Aim:</b> Symptoms of autonomic failure are frequently the presentation of advanced age and neurodegenerative diseases that impair adaptation to common physiologic stressors. The aim of this work was to examine the interaction between the sympathetic and motor nervous system, the involvement of the sympathetic nervous system (SNS) in neuromuscular junction (NMJ) presynaptic motor function, the stability of postsynaptic molecular organization, and the skeletal muscle composition and function. <b>Methods:</b> Since muscle weakness is a symptom of diseases characterized by autonomic dysfunction, we studied the impact of regional sympathetic ablation on muscle motor innervation by using transcriptome analysis, retrograde tracing of the sympathetic outflow to the skeletal muscle, confocal and electron microscopy, NMJ transmission by electrophysiological methods, protein analysis, and state of the art microsurgical techniques, in C57BL6, MuRF1KO and Thy-1 mice. <b>Results:</b> We found that the SNS regulates motor nerve synaptic vesicle release, skeletal muscle transcriptome, muscle force generated by motor nerve activity, axonal neurofilament phosphorylation, myelin thickness, and myofibre subtype composition and CSA. The SNS also modulates the levels of postsynaptic membrane acetylcholine receptor by regulating the Gαi2 -Hdac4-Myogenin-MuRF1pathway, which is prevented by the overexpression of the guanine nucleotide-binding protein Gαi2 (Q205L), a constitutively active mutant G protein subunit. <b>Conclusion:</b> The SNS regulates NMJ transmission, maintains optimal Gαi2 expression, and prevents any increase in Hdac4, myogenin, MuRF1, and miR-206. SNS ablation leads to upregulation of MuRF1, muscle atrophy, and downregulation of postsynaptic AChR. Our findings are relevant to clinical conditions characterized by progressive decline of sympathetic innervation, such as neurodegenerative diseases and aging.
format Articulo
Preprint
author Zaia Rodrigues, Anna Carolina
Messi, María Laura
Wang, Zhong-Min
Abba, Martín Carlos
Pereyra, Andrea S.
Birbrair, Alexander
Zhang, Tan
O’Meara, Meaghan
Kwan, Ping
Silva López, Elsa Idaliz
Willis, Monte S.
Mintz, Akiva
Files, D. Clark
Furdui, Cristina M.
Oppenheim, Ronald W.
Delbono, Osvaldo
author_facet Zaia Rodrigues, Anna Carolina
Messi, María Laura
Wang, Zhong-Min
Abba, Martín Carlos
Pereyra, Andrea S.
Birbrair, Alexander
Zhang, Tan
O’Meara, Meaghan
Kwan, Ping
Silva López, Elsa Idaliz
Willis, Monte S.
Mintz, Akiva
Files, D. Clark
Furdui, Cristina M.
Oppenheim, Ronald W.
Delbono, Osvaldo
author_sort Zaia Rodrigues, Anna Carolina
title The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability
title_short The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability
title_full The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability
title_fullStr The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability
title_full_unstemmed The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability
title_sort sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/127183
https://onlinelibrary.wiley.com/doi/10.1111/apha.13195
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