PMID- 26733679
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20170922
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 113
IP  - 3
DP  - 2016 Jan 19
TI  - Sympathetic innervation controls homeostasis of neuromuscular junctions in health
      and disease.
PG  - 746-50
LID - 10.1073/pnas.1524272113 [doi]
AB  - 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 beta2-adrenoreceptor (ADRB2), cAMP production, and import of 
      the transcriptional coactivator peroxisome proliferator-activated receptor
      gamma-coactivator 1alpha (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.
FAU - Khan, Muzamil Majid
AU  - Khan MM
AD  - Interdisciplinary Center for Neurosciences, Universitat 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;
FAU - Lustrino, Danilo
AU  - Lustrino D
AD  - Department of Physiology, Faculdade de Medicina de Ribeirao Preto, University of 
      Sao Paulo, 14049-900 Ribeirao Preto, Brazil; Department of Biochemistry and
      Immunology, Faculdade de Medicina de Ribeirao Preto, University of Sao Paulo,
      14049-900 Ribeirao Preto, Brazil;
FAU - Silveira, Willian A
AU  - Silveira WA
AD  - Department of Physiology, Faculdade de Medicina de Ribeirao Preto, University of 
      Sao Paulo, 14049-900 Ribeirao Preto, Brazil; Department of Biochemistry and
      Immunology, Faculdade de Medicina de Ribeirao Preto, University of Sao Paulo,
      14049-900 Ribeirao Preto, Brazil;
FAU - Wild, Franziska
AU  - Wild F
AD  - Interdisciplinary Center for Neurosciences, Universitat 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;
FAU - Straka, Tatjana
AU  - Straka T
AD  - Interdisciplinary Center for Neurosciences, Universitat 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;
FAU - Issop, Yasmin
AU  - Issop Y
AD  - The John Walton Muscular Dystrophy Research Centre, Medical Research Council
      Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne NE1 
      3BZ, United Kingdom;
FAU - O'Connor, Emily
AU  - O'Connor E
AD  - The John Walton Muscular Dystrophy Research Centre, Medical Research Council
      Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne NE1 
      3BZ, United Kingdom;
FAU - Cox, Dan
AU  - Cox D
AD  - The John Walton Muscular Dystrophy Research Centre, Medical Research Council
      Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne NE1 
      3BZ, United Kingdom;
FAU - Reischl, Markus
AU  - Reischl M
AD  - Institute of Applied Informatics, Karlsruhe Institute of Technology, 76344
      Eggenstein-Leopoldshafen, Germany;
FAU - Marquardt, Till
AU  - Marquardt T
AD  - Developmental Neurobiology Laboratory, European Neuroscience Institute, 37077
      Gottingen, Germany;
FAU - Labeit, Dittmar
AU  - Labeit D
AD  - Department of Integrative Pathophysiology, Universitat Heidelberg, 68167
      Mannheim, Germany;
FAU - Labeit, Siegfried
AU  - Labeit S
AD  - Department of Integrative Pathophysiology, Universitat Heidelberg, 68167
      Mannheim, Germany;
FAU - Benoit, Evelyne
AU  - Benoit E
AD  - Commissariat a l'energie atomique, Institut de Biologie et Technologies de Saclay
      (iBiTec-S), Service d'Ingenierie Moleculaire des Proteines (SIMOPRO), 91191
      Gif-sur-Yvette Cedex, France; Institut des Neurosciences Paris-Saclay, UMR 9197, 
      CNRS/Universite Paris-Sud, 91190 Gif-sur-Yvette Cedex, France;
FAU - Molgo, Jordi
AU  - Molgo J
AD  - Commissariat a l'energie atomique, Institut de Biologie et Technologies de Saclay
      (iBiTec-S), Service d'Ingenierie Moleculaire des Proteines (SIMOPRO), 91191
      Gif-sur-Yvette Cedex, France; Institut des Neurosciences Paris-Saclay, UMR 9197, 
      CNRS/Universite Paris-Sud, 91190 Gif-sur-Yvette Cedex, France;
FAU - Lochmuller, Hanns
AU  - Lochmuller H
AD  - The John Walton Muscular Dystrophy Research Centre, Medical Research Council
      Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne NE1 
      3BZ, United Kingdom;
FAU - Witzemann, Veit
AU  - Witzemann V
AD  - Max Planck Institute for Medical Research, 69120 Heidelberg, Germany;
FAU - Kettelhut, Isis C
AU  - Kettelhut IC
AD  - Department of Physiology, Faculdade de Medicina de Ribeirao Preto, University of 
      Sao Paulo, 14049-900 Ribeirao Preto, Brazil; Department of Biochemistry and
      Immunology, Faculdade de Medicina de Ribeirao Preto, University of Sao Paulo,
      14049-900 Ribeirao Preto, Brazil;
FAU - Navegantes, Luiz C C
AU  - Navegantes LC
AD  - Department of Physiology, Faculdade de Medicina de Ribeirao Preto, University of 
      Sao Paulo, 14049-900 Ribeirao Preto, Brazil; Department of Biochemistry and
      Immunology, Faculdade de Medicina de Ribeirao Preto, University of Sao Paulo,
      14049-900 Ribeirao Preto, Brazil;
FAU - Pozzan, Tullio
AU  - Pozzan T
AD  - Department of Biomedical Sciences, University of Padua, 35121 Padua, Italy;
      Institute of Neuroscience, Padua Section, National Research Council, 35121 Padua,
      Italy tullio.pozzan@unipd.it r.rudolf@hs-mannheim.de.
FAU - Rudolf, Rudiger
AU  - Rudolf R
AD  - Interdisciplinary Center for Neurosciences, Universitat 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;
      tullio.pozzan@unipd.it r.rudolf@hs-mannheim.de.
LA  - eng
GR  - MR/K000608/1/Medical Research Council/United Kingdom
GR  - 98482/Medical Research Council/United Kingdom
GR  - G1002274/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160105
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Transcription Factors)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
EIN - Proc Natl Acad Sci U S A. 2017 Jun 19;:. PMID: 28630297
MH  - Active Transport, Cell Nucleus
MH  - Animals
MH  - Biosensing Techniques
MH  - Cell Nucleus/metabolism
MH  - Cyclic AMP/metabolism
MH  - Female
MH  - *Health
MH  - *Homeostasis
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Muscle, Skeletal/innervation
MH  - Nervous System Diseases/*pathology
MH  - Neuromuscular Junction/metabolism/*pathology
MH  - Neurons/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Phenotype
MH  - Signal Transduction
MH  - Sympathectomy
MH  - Sympathetic Nervous System/metabolism/*pathology
MH  - Transcription Factors/metabolism
PMC - PMC4725522
OTO - NOTNLM
OT  - beta-agonists
OT  - cAMP
OT  - myasthenia
OT  - neuromuscular junction
OT  - sympathetic neurons
EDAT- 2016/01/07 06:00
MHDA- 2016/06/15 06:00
CRDT- 2016/01/07 06:00
PHST- 2016/01/07 06:00 [entrez]
PHST- 2016/01/07 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
AID - 1524272113 [pii]
AID - 10.1073/pnas.1524272113 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):746-50. doi:
      10.1073/pnas.1524272113. Epub 2016 Jan 5.