Increased Cholinergic Tone Causes Pre-synaptic Neuromuscular Degeneration and is Associated with Impaired Diaphragm Function

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Autor(es): dc.contributorUniversidade Federal de Minas Gerais (UFMG)-
Autor(es): dc.contributorUFJF-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversity of Western Ontario-
Autor(es): dc.contributorFCMMG-
Autor(es): dc.creatorMagalhães-Gomes, Matheus P.S.-
Autor(es): dc.creatorCamargos, Wallace-
Autor(es): dc.creatorValadão, Priscila A.C.-
Autor(es): dc.creatorGarcias, Rubens S.-
Autor(es): dc.creatorRodrigues, Hermann A.-
Autor(es): dc.creatorAndrade, Jéssica N.-
Autor(es): dc.creatorTeixeira, Vanessa P.-
Autor(es): dc.creatorNaves, Lígia A.-
Autor(es): dc.creatorCavalcante, Walter L.G.-
Autor(es): dc.creatorGallaci, Marcia [UNESP]-
Autor(es): dc.creatorGuatimosim, Silvia-
Autor(es): dc.creatorPrado, Vânia F.-
Autor(es): dc.creatorPrado, Marco A.M.-
Autor(es): dc.creatorGuatimosim, Cristina-
Data de aceite: dc.date.accessioned2022-02-22T00:50:08Z-
Data de disponibilização: dc.date.available2022-02-22T00:50:08Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-04-15-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.neuroscience.2020.12.025-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/207399-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/207399-
Descrição: dc.descriptionIn vertebrates, muscle activity is dependent on acetylcholine (ACh) released from neuromuscular junctions (NMJs), and changes in cholinergic neurotransmission are linked to a variety of neuromuscular diseases, including congenital myasthenic syndromes (CMS). The storage and release of ACh depends on the activity of the Vesicular Acetylcholine Transporter (VAChT), a rate-limiting step for cholinergic neurotransmission whose loss of function mutations was shown to cause human congenital myasthenia. However, we know much less about increased VAChT activity, due to copy number variations, for example. Therefore, here we investigated the impact of increased VAChT expression and consequently ACh levels at the synaptic cleft of the diaphragm NMJs. We analyzed structure and function of nerve and muscles from a mouse model of cholinergic hyperfunction (ChAT-ChR2-EYFP) with increased expression of VAChT. Our results showed a significant increase of ACh released under evoked stimuli. However, we observed deleterious changes in synaptic vesicles cycle (impaired endocytosis and decrease in vesicles number), together with structural alterations of NMJs. Interestingly, ultrastructure analyses showed that synaptic vesicles from ChAT-ChR2-EYFP mice NMJs were larger, which might be related to increased ACh load. We also observed that these larger synaptic vesicles were less rounded in comparison with control. Finally, we showed that ChAT-ChR2-EYFP mice NMJs have compromised safety factor, possible due to the structural alterations we described. These findings reveal that physiological cholinergic activity is important to maintain the structure and function of the neuromuscular system and help to understand some of the neuromuscular adverse effects experienced by chronically increased NMJ neurotransmission, such as individuals treated with cholinesterase inhibitors.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)-
Descrição: dc.descriptionDepartamento de Morfologia ICB Universidade Federal de Minas Gerais-
Descrição: dc.descriptionDepartamento de Fisiologia e Biofísica ICB Universidade Federal de Minas Gerais-
Descrição: dc.descriptionDepartamento de Farmacologia ICB Universidade Federal de Minas Gerais-
Descrição: dc.descriptionDepartamento de Ciências Básicas da Vida Instituto de Ciências da Vida Universidade Federal de Juiz de Fora Campus Governador Valadares UFJF-
Descrição: dc.descriptionDepartamento de Farmacologia Instituto de Biociências UNESP, Distrito de Rubião Jr.-
Descrição: dc.descriptionRobarts Research Institute and Department of Physiology and Pharmacology and Anatomy & Cell Biology University of Western Ontario-
Descrição: dc.descriptionDepartamento de Medicina Faculdade Ciências Médicas de Minas Gerais FCMMG-
Descrição: dc.descriptionDepartamento de Farmacologia Instituto de Biociências UNESP, Distrito de Rubião Jr.-
Descrição: dc.descriptionCNPq: 150567/2019-7-
Descrição: dc.descriptionCNPq: 401071/2014-6-
Descrição: dc.descriptionFAPEMIG: APQ-00092-18-
Formato: dc.format31-42-
Idioma: dc.languageen-
Relação: dc.relationNeuroscience-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectacetylcholine-
Palavras-chave: dc.subjectcholinergic signaling-
Palavras-chave: dc.subjectneuromuscular junction-
Título: dc.titleIncreased Cholinergic Tone Causes Pre-synaptic Neuromuscular Degeneration and is Associated with Impaired Diaphragm Function-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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