Abstract:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Dysfunction of neuromuscular synapses is one of the earliest and most important events in the pathogenesis of amyotrophic lateral sclerosis (ALS). The present study was aimed to investigate the abundance of major synaptic proteins (synaptophysin, SNAP-25, synapsin I, nicotinic acetylcholine receptors) in the neuromuscular synapses of the diaphragm of mSOD1 transgenic mice with ALS model. Even in the presymptomatic stage of pathology, significant decrease of SNAP-25 and synapsin I abundance was found in neuromuscular synapses of mSOD1 mice, which can underlie synaptic dysfunctions described in previous studies. In the symptomatic mSOD1 mice, the immunoexpression of all studied presynaptic proteins was markedly decreased, as well as decrease in the degree of co-localization of the areas of expression of synaptophysin, and nicotinic acetylcholine receptors was shown. Thus, the molecular aspects of neuromuscular synapses dysfunction in different stages of modeled ALS in mSOD1 mice were described, which expands our understanding of the mechanisms of the ALS pathogenesis.
