Muscle & nerve · 2019
Evaluation of the neuromuscular junction in a middle-aged mouse model of congenital myasthenic syndrome.
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Leite Schetino Luana Pereira, de Castro Fonseca Matheus, Magalhães Gomes Matheus Proença Simão, Costa Valadão Priscila Aparecida, de Camargo Wallace Lucio, Rodrigues Hermann Alecsandro, Andrade Jéssica Neves, Arantes-Costa Fernanda Magalhães, Naves Lígia Araujo, Prado Carla Máximo, Prado Vânia Ferreira, Prado Marco Antônio Máximo, Guatimosim Cristina
Аннотация
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 VAChTKDHOM mice.
RESULTS: Diaphragms of NMJs of the VAChTKDHOM 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.
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 VAChTKDHOM mice.
RESULTS: Diaphragms of NMJs of the VAChTKDHOM 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.
Предметные рубрики MeSH
AcetylcholineAgingAnimalsDiaphragmDisease Models, AnimalEndocytosisExcitatory Postsynaptic PotentialsExocytosisGene Knockdown TechniquesMiceMicroscopy, ConfocalMicroscopy, Electron, TransmissionMotor EndplateMyasthenic Syndromes, CongenitalNeuromuscular JunctionRespiratory MechanicsSynaptic TransmissionSynaptic VesiclesVesicular Acetylcholine Transport Proteins