title: Changes in structure and function of diaphragm neuromuscular junctions from BACHD mouse model for Huntington's disease.
abstract: Huntington's disease (HD) is a neurodegenerative disorder characterized by a progressive decline of motor and cognitive functions. It is caused by a polyglutamine expansion in the huntingtin (htt) protein, which then leads to neurodegeneration that span both the central and peripheral nervous system. Previous works have shown that htt interacts with several proteins from the neurotransmitter release machinery causing synaptic dysfunction. In this work, we looked for alterations in diaphragm neuromuscular junctions (NMJs) from 3 to 4 months old BACHD mouse model for HD. This model represents a new and robust in vivo paradigm for studying the pathogenesis of HD. For optical analysis, NMJs were stained with FM1-43fx and α-bungarotoxin to visualize both pre and postsynaptic elements, respectively. Confocal microscopy optical analysis showed a decrease in the number of synaptic elements and fluorescence intensity in NMJs from BACHD diaphragms compared to WT. We next analyzed presynaptic activity and we observed that synaptic vesicle exocytosis was impaired in NMJs from BACHD diaphragms. Ultrastructural analysis revealed significant changes in the form and sizes of the synaptic vesicles in BACHD diaphragm NMJs that could contribute to impaired exocytosis. Additionally, electrophysiology recordings revealed a decrease in the amplitude of miniature endplate potentials (MEPPs) from BACHD diaphragm NMJs. Our data suggest a dysfunction in BACHD diaphragm NMJs that might occur in other muscles and may aggravate the motor defects seen in HD. These results may contribute to a better understanding of peripheral cholinergic dysfunction in this neurodegenerative disease.
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Bárbara Campos
authors.initials: BC
authors.lastname: de Aragão
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Hermann Alecsandro
authors.initials: HA
authors.lastname: Rodrigues
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Priscila Aparecida Costa
authors.initials: PA
authors.lastname: Valadão
authors.affiliation: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Wallace
authors.initials: W
authors.lastname: Camargo
authors.affiliation: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Lígia Araujo
authors.initials: LA
authors.lastname: Naves
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Fabíola Mara
authors.initials: FM
authors.lastname: Ribeiro
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address: cguati@icb.ufmg.br.
authors.forename: Cristina
authors.initials: C
authors.lastname: Guatimosim
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000294:innervation*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000378:metabolism*; D051379:Mice; D009469:Neuromuscular Junction / Q000378:metabolism*
keywords: BACHD; Exocytosis; Huntington disease; Neuromuscular junction; Synaptic vesicles