The p75(NTR) neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availability

ACTA NEUROPATHOLOGICA COMMUNICATIONS

dc.creatorPérez, Viviana
dc.creatorBermedo-Garcia, Francisca
dc.creatorZelada, Diego
dc.creatorCourt-Goldsmith, Felipe Alfredo
dc.creatorPérez, Miguel Ángel
dc.creatorFuenzalida, Marco
dc.creatorAbrigo, Johanna
dc.creatorCabello-Verrugio, Claudio
dc.creatorMoya-Alvarado, Guillermo
dc.creatorTapia, Juan Carlos
dc.creatorValenzuela, Vicente
dc.creatorHetz, Claudio
dc.creatorBronfman, Francisca C
dc.creatorHenriquez, Juan Pablo
dc.date2021-08-23T22:51:19Z
dc.date2022-07-08T20:28:44Z
dc.date2021-08-23T22:51:19Z
dc.date2022-07-08T20:28:44Z
dc.date2019
dc.date.accessioned2023-08-21T21:27:10Z
dc.date.available2023-08-21T21:27:10Z
dc.identifier1150766
dc.identifier1150766
dc.identifierhttps://hdl.handle.net/10533/250757
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8284417
dc.descriptionThe 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 p75(NTR) pan-neurotrophin receptor. Even though p75(NTR) targeting has emerged as a promising therapeutic strategy to delay peripheral neuronal damage progression, the effects of long-term p75(NTR) inhibition at the mature neuromuscular junction have not been elucidated. We performed quantitative neuroanathomical analyses of the neuromuscular junction in p75(NTR) null mice by laser confocal and electron microscopy, which were complemented with electromyography, locomotor tests, and pharmacological intervention studies. Mature neuromuscular synapses of p75(NTR) 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 p75(NTR) does not play a major role on postsynaptic organization. In turn, motor axon terminals of p75(NTR) 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 p75(NTR) null mice. Our findings revealing that p75(NTR) is required to organize mature neuromuscular junctions contribute to a comprehensive view of the possible effects caused by therapeutic attempts to target p75(NTR).
dc.descriptionRegular 2015
dc.descriptionFONDECYT
dc.descriptionFONDECYT
dc.languageeng
dc.relationhandle/10533/111557
dc.relationhandle/10533/111541
dc.relationhandle/10533/108045
dc.relationhttps://doi.org/10.1186/s40478-019-0802-7
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/article
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleThe p75(NTR) neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availability
dc.titleACTA NEUROPATHOLOGICA COMMUNICATIONS
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/publishedVersion


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