Evaluation of the neuromuscular junction in a middle-aged mouse model of congenital myasthenic syndrome
Luana Pereira Leite Schetino MS, PhD
Faculdade de Medicina, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais, Brazil
Search for more papers by this authorMatheus de Castro Fonseca MS, PhD
Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil
Search for more papers by this authorMatheus Proença Simão Magalhães Gomes MS, PhD
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorPriscila Aparecida Costa Valadão MS, PhD
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorWallace Lucio de Camargo MS
Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorHermann Alecsandro Rodrigues MS, PhD
Departamento de Ciências Básicas da Vida, Instituto de Ciências da Vida, Universidade Federal de Juiz de Fora, Campus Governador Valadares, Minas Gerais, Brazil
Search for more papers by this authorJéssica Neves Andrade MS
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorFernanda Magalhães Arantes-Costa MS, PhD
Departamento de Medicina, Escola de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil
Search for more papers by this authorLígia Araujo Naves MS, PhD
Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorCarla Máximo Prado PhD
Departmento de Biociências, Universidade Federal de São Paulo, Campus Baixada Santista, São Paulo, Brazil
Search for more papers by this authorVânia Ferreira Prado PhD
Robarts Research Institute and Department of Physiology and Pharmacology and Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorMarco Antônio Máximo Prado MS, PhD
Robarts Research Institute and Department of Physiology and Pharmacology and Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorCorresponding Author
Cristina Guatimosim PhD
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Correspondence
Cristina Guatimosim, Universidade Federal de Minas Gerais, Av Pres Antônio Carlos, Belo Horizonte, 6627 MG, 31270-901, Brazil.
Email: [email protected]
Search for more papers by this authorLuana Pereira Leite Schetino MS, PhD
Faculdade de Medicina, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais, Brazil
Search for more papers by this authorMatheus de Castro Fonseca MS, PhD
Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil
Search for more papers by this authorMatheus Proença Simão Magalhães Gomes MS, PhD
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorPriscila Aparecida Costa Valadão MS, PhD
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorWallace Lucio de Camargo MS
Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorHermann Alecsandro Rodrigues MS, PhD
Departamento de Ciências Básicas da Vida, Instituto de Ciências da Vida, Universidade Federal de Juiz de Fora, Campus Governador Valadares, Minas Gerais, Brazil
Search for more papers by this authorJéssica Neves Andrade MS
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorFernanda Magalhães Arantes-Costa MS, PhD
Departamento de Medicina, Escola de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil
Search for more papers by this authorLígia Araujo Naves MS, PhD
Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Search for more papers by this authorCarla Máximo Prado PhD
Departmento de Biociências, Universidade Federal de São Paulo, Campus Baixada Santista, São Paulo, Brazil
Search for more papers by this authorVânia Ferreira Prado PhD
Robarts Research Institute and Department of Physiology and Pharmacology and Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorMarco Antônio Máximo Prado MS, PhD
Robarts Research Institute and Department of Physiology and Pharmacology and Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorCorresponding Author
Cristina Guatimosim PhD
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Correspondence
Cristina Guatimosim, Universidade Federal de Minas Gerais, Av Pres Antônio Carlos, Belo Horizonte, 6627 MG, 31270-901, Brazil.
Email: [email protected]
Search for more papers by this authorFunding information: Conselho Nacional de Desenvolvimento Científico e Tecnológico; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Fundação de Amparo à Pesquisa do Estado de Minas Gerais; Fundação de Amparo à Pesquisa do Estado de São Paulo, Grant/Award Number: 2018/20014-0
Abstract
Introduction
Reduced expression of the vesicular acetylcholine transporter (VAChT) leads to changes in the distribution and shape of synaptic vesicles (SVs) at neuromuscular junctions (NMJs), suggesting vesicular acetylcholine (ACh) as a key component of synaptic structure and function. It is poorly understood how long-term changes in cholinergic transmission contribute to age- and disease-related degeneration in the motor system.
Methods
In this study we performed confocal imaging, electrophysiology, electron microscopy, and analyses of respiratory mechanics of the diaphragm NMJ components in 12-month-old wild-type (WT) and VAChTKDHOM mice.
Results
Diaphragms of NMJs of the VAChTKDHOM mice were similar to those in WT mice in number, colocalization, and fragmentation of pre−/postsynaptic components. However, they had increased spontaneous SV exocytosis, miniature endplate potential frequency, and diminished MEPP amplitude. No impairment in respiratory mechanics at rest was observed, probably due to the large neurotransmission safety factor of the diaphragm.
Discussion
The present findings help us to understand the consequences of reduced ACh release at the NMJs during aging.
CONFLICT OF INTEREST
The authors declare no potential conflicts of interest.
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