title: Aerobic training attenuates nicotinic acethylcholine receptor changes in the diaphragm muscle during heart failure.
abstract: BACKGROUND
  Heart failure (HF) is a progressive myopathy, with clinical signs of fatigue and limb weakness that can damage the nerve-muscle interaction, altering synaptic transmission and nicotinic acetylcholine receptors (nAChR) in neuromuscular junctions (NMJs). The diaphragm is composed of a mixed proportion of muscle fibres, and during HF, this muscle becomes slower and can alter its function. As exercise training is an accepted practice to minimise abnormalities of skeletal muscle during HF, in this study, we evaluated the hypothesis that aerobic training attenuates alterations in the expression of nAChR subunits in NMJs diaphragm during heart failure.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the distribution and expression of nAChR subunits in the diaphragm muscle fibres of rats subjected to an aerobic training programme during HF.
  
  
  METHODS
  Control (Sham), control training (ShamTR), aortic stenosis (AS) and aortic stenosis training (ASTR) groups were evaluated. The expression of nAChR subunits (γ, α1, ε, β1 and δ) was determined by qRT-PCR, and NMJs were analysed using confocal microscopy.
  
  
  RESULTS
  We observed increased expression of the γ, α1 and β1 subunits in the AS group compared with the ASTR group. The distribution of NMJs was modulated in these groups.
  
  
  CONCLUSIONS
  HF alters the mRNA expression of nAChR subunits and the structural characteristics of diaphragm NMJs. In addition, aerobic training did not alter NMJs morphology but attenuated the alterations in heart structure and function and in nAChR subunit mRNA expression. Our findings demonstrate the beneficial effects of aerobic exercise training in maintaining the integrity of the neuromuscular system in the diaphragm muscle during HF and may be critical for non-pharmacological therapy to improve the quality of life for patients with this syndrome.
authors.affiliation: Department of Morphology, Bioscience Institute, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Paula Aiello Tomé
authors.initials: PA
authors.lastname: de Souza
authors.affiliation: Department of Morphology, Bioscience Institute, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Rodrigo Wagner Alves
authors.initials: RW
authors.lastname: de Souza
authors.affiliation: Department of Morphology, Bioscience Institute, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Luana Campos
authors.initials: LC
authors.lastname: Soares
authors.affiliation: Department of Morphology, Bioscience Institute, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Warlen Pereira
authors.initials: WP
authors.lastname: Piedade
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Dijon Henrique S
authors.initials: DH
authors.lastname: Campos
authors.affiliation: Department of Morphology, Bioscience Institute, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Robson Francisco
authors.initials: RF
authors.lastname: Carvalho
authors.affiliation: Department of Statistic, Bioscience Institute, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Carlos Roberto
authors.initials: CR
authors.lastname: Padovani
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Katashi
authors.initials: K
authors.lastname: Okoshi
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Antônio Carlos
authors.initials: AC
authors.lastname: Cicogna
authors.affiliation: Department of Anatomy, Bioscience Institute, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.
authors.forename: Selma Maria Michelin
authors.initials: SM
authors.lastname: Matheus
authors.affiliation: Department of Morphology, Bioscience Institute, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil. maeli@ibb.unesp.br.
authors.forename: Maeli
authors.initials: M
authors.lastname: Dal-Pai-Silva
mesh_terms: D000332:Aerobiosis; D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications / Q000378:metabolism / Q000628:therapy; D003964:Diaphragm / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D010805:Physical Conditioning, Animal / Q000379:methods*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D011978:Receptors, Nicotinic