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Evaluation of the neuromuscular junction in a middle‐aged mouse model of congenital myasthenic syndrome
Author(s) -
Leite Schetino Luana Pereira,
Fonseca Matheus,
Magalhães Gomes Matheus Proença Simão,
Costa Valadão Priscila Aparecida,
Camargo Wallace Lucio,
Rodrigues Hermann Alecsandro,
Andrade Jéssica Neves,
ArantesCosta Fernanda Magalhães,
Naves Lígia Araujo,
Prado Carla Máximo,
Prado Vânia Ferreira,
Prado Marco Antônio Máximo,
Guatimosim Cristina
Publication year - 2019
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26710
Subject(s) - neuromuscular junction , neuromuscular transmission , synaptic vesicle , acetylcholine , neuroscience , postsynaptic potential , cholinergic , neurotransmission , synapse , colocalization , motor endplate , synaptic cleft , biology , diaphragm (acoustics) , vesicular acetylcholine transporter , neurotransmitter , medicine , endocrinology , vesicle , choline acetyltransferase , central nervous system , biochemistry , physics , receptor , membrane , acoustics , loudspeaker
Abstract Introduction Reduced expression of the vesicular acetylcholine transporter (VAChT) leads to changes in the distribution and shape of synaptic vesicles (SVs) at neuromuscular junctions (NMJs), suggesting vesicular acetylcholine (ACh) as a key component of synaptic structure and function. It is poorly understood how long‐term changes in cholinergic transmission contribute to age‐ and disease‐related degeneration in the motor system. Methods In this study we performed confocal imaging, electrophysiology, electron microscopy, and analyses of respiratory mechanics of the diaphragm NMJ components in 12‐month‐old wild‐type (WT) and VAChTKD HOM mice. Results Diaphragms of NMJs of the VAChTKD HOM mice were similar to those in WT mice in number, colocalization, and fragmentation of pre−/postsynaptic components. However, they had increased spontaneous SV exocytosis, miniature endplate potential frequency, and diminished MEPP amplitude. No impairment in respiratory mechanics at rest was observed, probably due to the large neurotransmission safety factor of the diaphragm. Discussion The present findings help us to understand the consequences of reduced ACh release at the NMJs during aging.