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

Valadão, Priscila A.C. et al.

Neurochemistry international. Volume 116:(2018):no.; 201806; 30-42 -- Elsevier

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  • Title:
    Neuromuscular synapse degeneration without muscle function loss in the diaphragm of a murine model for Huntington's Disease
  • Author: 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;
    de Jesus, Itamar C.G.;
    Guatimosim, Silvia;
    Guatimosim, Cristina
  • Found In: Neurochemistry international. Volume 116:(2018):no.; 201806; 30-42
  • Journal Title: Neurochemistry international
  • Subjects: Neurochemistry; Neurochemistry; Neurochimie Périodiques; Neurochemistry; LCSH: Neurochemistry; Dewey: 612.804205
  • Rights: Licensed
  • Publication Details: Elsevier
  • Abstract: 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.HighlightsAxons from the phrenic nerve were not affected in 12-months-old BACHD mice but axon terminals (NMJs) were more fragmented.Synaptic vesicles from the NMJs of BACHD presented decreased exocytosis rate, abnormal shape and released less acetylcholine.Diaphragm muscle mitochondria presented signs of degeneration in BACHD altough muscle function was preserved.
  • Identifier: Journal ISSN: 0197-0186
  • Publication Date: 2018
  • Physical Description: Electronic
  • Shelfmark(s): ELD Digital store
    6081.317000
  • UIN: ETOCvdc_100057065538.0x000001

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