Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease

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dc.contributor.authorValadão, Priscila A.C.
dc.contributor.authorGomes, Matheus P.S.M.
dc.contributor.authorAragão, Bárbara C.
dc.contributor.authorRodrigues, Hermann A.
dc.contributor.authorAndrade, Jéssica N.
dc.contributor.authorGarcias, Rubens
dc.contributor.authorJoviano-Santos, Julliane V.
dc.contributor.authorLuiz, Murilo A.
dc.contributor.authorCamargo, Wallace L.
dc.contributor.authorNaves, Lígia A.
dc.contributor.authorKushmerick, Christopher
dc.contributor.authorCavalcante, Walter L.G.
dc.contributor.authorGallacci, Márcia [UNESP]
dc.contributor.authorde Jesus, Itamar C.G.
dc.contributor.authorGuatimosim, Silvia
dc.contributor.authorGuatimosim, Cristina
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionGV
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-12-11T17:18:29Z
dc.date.available2018-12-11T17:18:29Z
dc.date.issued2018-06-01
dc.description.abstractHuntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by chorea, incoordination and psychiatric and behavioral symptoms. The leading cause of death in HD patients is aspiration pneumonia, associated with respiratory dysfunction, decreased respiratory muscle strength and dysphagia. Although most of the motor symptoms are derived from alterations in the central nervous system, some might be associated with changes in the components of motor units (MU). To explore this hypothesis, we evaluated morphofunctional aspects of the diaphragm muscle in a mouse model for HD (BACHD). We showed that the axons of the phrenic nerves were not affected in 12-months-old BACHD mice, but the axon terminals that form the neuromuscular junctions (NMJs) were more fragmented in these animals in comparison with the wild-type mice. In BACHD mice, the synaptic vesicles of the diaphragm NMJs presented a decreased exocytosis rate. Quantal content and quantal size were smaller and there was less synaptic depression whereas the estimated size of the readily releasable vesicle pool was not changed. At the ultrastructure level, the diaphragm NMJs of these mice presented fewer synaptic vesicles with flattened and oval shapes, which might be associated with the reduced expression of the vesicular acetylcholine transporter protein. Furthermore, mitochondria of the diaphragm muscle presented signs of degeneration in BACHD mice. Interestingly, despite all these cellular alterations, BACHD diaphragmatic function was not compromised, suggesting a higher resistance threshold of this muscle. A putative resistance mechanism may be protecting this vital muscle. Our data contribute to expanding the current understanding of the effects of mutated huntingtin in the neuromuscular synapse and the diaphragm muscle function.en
dc.description.affiliationDepartamento de Morfologia Universidade Federal de Minas Gerais
dc.description.affiliationDepartamento de Fisiologia e Biofísica Universidade Federal de Minas Gerais
dc.description.affiliationDepartamento de Farmacologia Universidade Federal de Minas Gerais
dc.description.affiliationDepartamento de Ciências Básicas da Vida Instituto de Ciências da Vida Universidade Federal de Juiz de Fora Campus Governador Valadares UFJF GV
dc.description.affiliationDepartamento de Farmacologia Instituto de Biociências UNESP Distrito de Rubião Jr.
dc.description.affiliationUnespDepartamento de Farmacologia Instituto de Biociências UNESP Distrito de Rubião Jr.
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPEMIG: #00271-13
dc.description.sponsorshipIdCNPq: #467220/2014-0
dc.description.sponsorshipIdCNPq: #475735/2013-7
dc.format.extent30-42
dc.identifierhttp://dx.doi.org/10.1016/j.neuint.2018.03.007
dc.identifier.citationNeurochemistry International, v. 116, p. 30-42.
dc.identifier.doi10.1016/j.neuint.2018.03.007
dc.identifier.file2-s2.0-85043574016.pdf
dc.identifier.issn1872-9754
dc.identifier.issn0197-0186
dc.identifier.lattes9353490382598257
dc.identifier.scopus2-s2.0-85043574016
dc.identifier.urihttp://hdl.handle.net/11449/176002
dc.language.isoeng
dc.relation.ispartofNeurochemistry International
dc.relation.ispartofsjr1,283
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectBACHD
dc.subjectDiaphragm
dc.subjectHuntington's disease
dc.subjectNeuromuscular junctions
dc.titleNeuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Diseaseen
dc.typeArtigo
unesp.author.lattes9353490382598257
unesp.author.orcid0000-0002-9380-4192[6]

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