The p75NTR neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availability

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dc.contributor.authorPérez, Viviana
dc.contributor.authorBermedo-Garcia, Francisca
dc.contributor.authorZelada, Diego
dc.contributor.authorCourt, Felipe A.
dc.contributor.authorPérez, Miguel Ángel
dc.contributor.authorFuenzalida, Marco
dc.contributor.authorÁbrigo, Johanna
dc.contributor.authorCabello-Verrugio, Claudio
dc.contributor.authorMoya-Alvarado, Guillermo
dc.contributor.authorTapia, Juan Carlos
dc.contributor.authorValenzuela, Vicente
dc.contributor.authorHetz, Claudio
dc.contributor.authorBronfman, Francisca C.
dc.contributor.authorHenríquez, Juan Pablo
dc.date.accessioned2020-05-26T22:28:16Z
dc.date.available2020-05-26T22:28:16Z
dc.date.issued2019
dc.description.abstractThe coordinated movement of organisms relies on efficient nerve-muscle communication at the neuromuscular junction. After peripheral nerve injury or neurodegeneration, motor neurons and Schwann cells increase the expression of the p75NTR pan-neurotrophin receptor. Even though p75NTR targeting has emerged as a promising therapeutic strategy to delay peripheral neuronal damage progression, the effects of long-term p75NTR inhibition at the mature neuromuscular junction have not been elucidated. We performed quantitative neuroanathomical analyses of the neuromuscular junction in p75NTR null mice by laser confocal and electron microscopy, which were complemented with electromyography, locomotor tests, and pharmacological intervention studies. Mature neuromuscular synapses of p75NTR null mice show impaired postsynaptic organization and ultrastructural complexity, which correlate with altered synaptic function at the levels of nerve activity-induced muscle responses, muscle fiber structure, force production, and locomotor performance. Our results on primary myotubes and denervated muscles indicate that muscle-derived p75NTR does not play a major role on postsynaptic organization. In turn, motor axon terminals of p75NTR null mice display a strong reduction in the number of synaptic vesicles and active zones. According to the observed pre and postsynaptic defects, pharmacological acetylcholinesterase inhibition rescued nerve-dependent muscle response and force production in p75NTR null mice. Our findings revealing that p75NTR is required to organize mature neuromuscular junctions contribute to a comprehensive view of the possible effects caused by therapeutic attempts to target p75NTR.es_ES
dc.identifier.issn2051-5960
dc.identifier.other10.1186/s40478-019-0802-7
dc.identifier.urihttps://hdl.handle.net/20.500.12536/438
dc.language.isoenes_ES
dc.sourceActa Neuropathologica Communications
dc.subjectNeuromuscular junctiones_ES
dc.subjectp75NTRes_ES
dc.subjectNeurotrophines_ES
dc.subjectMotor neurones_ES
dc.subjectSynaptic vesicleses_ES
dc.titleThe p75NTR neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availabilityes_ES
dc.typeArtículo de revistaes_ES
uvm.escuelaEscuela de Ciencias de la Saludes_ES
uvm.indexScopuses_ES
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