Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.neuint.2018.03.007 http://hdl.handle.net/11449/176002 |
Resumo: | Huntington'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. |
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Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's DiseaseBACHDDiaphragmHuntington's diseaseNeuromuscular junctionsHuntington'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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Departamento de Morfologia Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biofísica Universidade Federal de Minas GeraisDepartamento de Farmacologia Universidade Federal de Minas GeraisDepartamento de Ciências Básicas da Vida Instituto de Ciências da Vida Universidade Federal de Juiz de Fora Campus Governador Valadares UFJF GVDepartamento de Farmacologia Instituto de Biociências UNESP Distrito de Rubião Jr.Departamento de Farmacologia Instituto de Biociências UNESP Distrito de Rubião Jr.FAPEMIG: #00271-13CNPq: #467220/2014-0CNPq: #475735/2013-7Universidade Federal de Minas Gerais (UFMG)GVUniversidade Estadual Paulista (Unesp)Valadão, Priscila A.C.Gomes, Matheus P.S.M.Aragão, Bárbara C.Rodrigues, Hermann A.Andrade, Jéssica N.Garcias, RubensJoviano-Santos, Julliane V.Luiz, Murilo A.Camargo, Wallace L.Naves, Lígia A.Kushmerick, ChristopherCavalcante, Walter L.G.Gallacci, Márcia [UNESP]de Jesus, Itamar C.G.Guatimosim, SilviaGuatimosim, Cristina2018-12-11T17:18:29Z2018-12-11T17:18:29Z2018-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article30-42application/pdfhttp://dx.doi.org/10.1016/j.neuint.2018.03.007Neurochemistry International, v. 116, p. 30-42.1872-97540197-0186http://hdl.handle.net/11449/17600210.1016/j.neuint.2018.03.0072-s2.0-850435740162-s2.0-85043574016.pdf9353490382598257Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNeurochemistry International1,283info:eu-repo/semantics/openAccess2024-01-10T06:30:21Zoai:repositorio.unesp.br:11449/176002Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-01-10T06:30:21Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease |
title |
Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease |
spellingShingle |
Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease Valadão, Priscila A.C. BACHD Diaphragm Huntington's disease Neuromuscular junctions |
title_short |
Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease |
title_full |
Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease |
title_fullStr |
Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease |
title_full_unstemmed |
Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease |
title_sort |
Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease |
author |
Valadão, Priscila A.C. |
author_facet |
Valadão, Priscila A.C. Gomes, Matheus P.S.M. Aragão, Bárbara C. Rodrigues, Hermann A. Andrade, Jéssica N. Garcias, Rubens Joviano-Santos, Julliane V. Luiz, Murilo A. Camargo, Wallace L. Naves, Lígia A. Kushmerick, Christopher Cavalcante, Walter L.G. Gallacci, Márcia [UNESP] de Jesus, Itamar C.G. Guatimosim, Silvia Guatimosim, Cristina |
author_role |
author |
author2 |
Gomes, Matheus P.S.M. Aragão, Bárbara C. Rodrigues, Hermann A. Andrade, Jéssica N. Garcias, Rubens Joviano-Santos, Julliane V. Luiz, Murilo A. Camargo, Wallace L. Naves, Lígia A. Kushmerick, Christopher Cavalcante, Walter L.G. Gallacci, Márcia [UNESP] de Jesus, Itamar C.G. Guatimosim, Silvia Guatimosim, Cristina |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de Minas Gerais (UFMG) GV Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Valadão, Priscila A.C. Gomes, Matheus P.S.M. Aragão, Bárbara C. Rodrigues, Hermann A. Andrade, Jéssica N. Garcias, Rubens Joviano-Santos, Julliane V. Luiz, Murilo A. Camargo, Wallace L. Naves, Lígia A. Kushmerick, Christopher Cavalcante, Walter L.G. Gallacci, Márcia [UNESP] de Jesus, Itamar C.G. Guatimosim, Silvia Guatimosim, Cristina |
dc.subject.por.fl_str_mv |
BACHD Diaphragm Huntington's disease Neuromuscular junctions |
topic |
BACHD Diaphragm Huntington's disease Neuromuscular junctions |
description |
Huntington'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. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-11T17:18:29Z 2018-12-11T17:18:29Z 2018-06-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.neuint.2018.03.007 Neurochemistry International, v. 116, p. 30-42. 1872-9754 0197-0186 http://hdl.handle.net/11449/176002 10.1016/j.neuint.2018.03.007 2-s2.0-85043574016 2-s2.0-85043574016.pdf 9353490382598257 |
url |
http://dx.doi.org/10.1016/j.neuint.2018.03.007 http://hdl.handle.net/11449/176002 |
identifier_str_mv |
Neurochemistry International, v. 116, p. 30-42. 1872-9754 0197-0186 10.1016/j.neuint.2018.03.007 2-s2.0-85043574016 2-s2.0-85043574016.pdf 9353490382598257 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Neurochemistry International 1,283 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
30-42 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965581985710080 |