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Influence of ß2-adrenergic selective agonist formoterol on the motor unit of a mouse model of a congenital myasthenic syndrome with complete VAChT deletion.
Rossi, Leonardo; Mota, Bárbara I; Valadão, Priscila A C; Magalhães-Gomes, Matheus P S; Oliveira, Bruna S; Guatimosim, Silvia; Navegantes, Luiz C C; Miranda, Aline S; Prado, Marco A M; Prado, Vânia F; Guatimosim, Cristina.
Afiliação
  • Rossi L; Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Mota BI; Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Valadão PAC; Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Magalhães-Gomes MPS; Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento de Ciências Básicas, Faculdade Ciências Médicas de Minas Gerais, FCMMG, Belo Horizonte, Brazil.
  • Oliveira BS; Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Guatimosim S; Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Navegantes LCC; Departamento de Fisiologia, Escola de Medicina, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Miranda AS; Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Prado MAM; Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada; Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada; Department of Physiology and Pharmacology, Schul
  • Prado VF; Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada; Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada; Department of Physiology and Pharmacology, Schul
  • Guatimosim C; Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: cguati@icb.ufmg.br.
Neuropharmacology ; 260: 110116, 2024 Dec 01.
Article em En | MEDLINE | ID: mdl-39151654
ABSTRACT
Congenital Myasthenic Syndromes (CMS) are a set of genetic diseases that affect the neuromuscular transmission causing muscular weakness. The standard pharmacological treatment aims at ameliorating the myasthenic symptom by acetylcholinesterase inhibitors. Most patients respond well in the short and medium term, however, over time the beneficial effects rapidly fade, and the efficacy of the treatment diminishes. Increasing evidence shows that ß2-adrenergic agonists can be a suitable choice for the treatment of neuromuscular disorders, including CMS, as they promote beneficial effects in the neuromuscular system. The exact mechanism on which they rely is not completely understood, although patients and animal models respond well to the treatment, especially over extended periods. Here, we report the use of the long-lasting specific ß2-adrenergic agonist formoterol in a myasthenic mouse model (mnVAChT-KD), featuring deletion of VAChT (Vesicular Acetylcholine Transporter) specifically in the α-motoneurons. Our findings demonstrate that formoterol treatment (300 µg/kg/day; sc) for 30 days increased the neuromuscular junction area, induced skeletal muscle hypertrophy and altered fibre type composition in myasthenic mice. Interestingly, ß2-adrenergic agonists have shown efficacy even in the absence of ACh (acetylcholine). Our data provide important evidence supporting the potential of ß2-adrenergic agonists in treating neuromuscular disorders of pre-synaptic origin and characterized by disruptions in nerve-muscle communication, through a direct and beneficial action within the motor unit.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndromes Miastênicas Congênitas / Modelos Animais de Doenças / Proteínas Vesiculares de Transporte de Acetilcolina / Agonistas de Receptores Adrenérgicos beta 2 / Fumarato de Formoterol / Junção Neuromuscular Limite: Animals Idioma: En Revista: Neuropharmacology Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndromes Miastênicas Congênitas / Modelos Animais de Doenças / Proteínas Vesiculares de Transporte de Acetilcolina / Agonistas de Receptores Adrenérgicos beta 2 / Fumarato de Formoterol / Junção Neuromuscular Limite: Animals Idioma: En Revista: Neuropharmacology Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido