N-Methyl-D-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection

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dc.creatorVivian Vasconcelos Costa
dc.creatorJulia Maria S. Araújo
dc.creatorAllysson Cramer
dc.creatorAna Luíza Campos Vila Real
dc.creatorLucas Secchim Ribeiro
dc.creatorSilvia Ines Sardi
dc.creatorAnderson J. Ferreira
dc.creatorFabiana Simão Machado
dc.creatorAntônio Costa de Oliveira
dc.creatorAntônio Lúcio Teixeira
dc.creatorHelder Nakaya
dc.creatorDanielle da Glória de Souza
dc.creatorFabiola M. Ribeiro
dc.creatorMauro Martins Teixeira
dc.creatorRebeca de Paiva Froes Rocha
dc.creatorFlavia R. Silva
dc.creatorJuliana G. Doria
dc.creatorIsabella Guimarães Olmo
dc.creatorRafael Elias Marques Pereira Silva
dc.creatorCelso Martins Queiroz Junior
dc.creatorGiselle Foureaux
dc.creatorJuliana Lemos Del Sarto
dc.date.accessioned2023-07-14T20:36:05Z
dc.date.accessioned2025-09-09T00:23:14Z
dc.date.available2023-07-14T20:36:05Z
dc.date.issued2017
dc.identifier.doihttps://doi.org/10.1128/mbio.00350-17
dc.identifier.issn2150-7511
dc.identifier.urihttps://hdl.handle.net/1843/56300
dc.languagepor
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofAmerican Society for Microbiology
dc.rightsAcesso Aberto
dc.subjectMedicina
dc.subjectMicrobiologia
dc.subjectPressão intra-ocular
dc.subject.otherNMDA receptor
dc.subject.otherZika virus
dc.subject.otherIntraocular pressure
dc.subject.otherMemantine
dc.subject.otherMicrogliosis
dc.subject.otherMouse model
dc.subject.otherNeuronal death
dc.titleN-Methyl-D-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection
dc.typeArtigo de evento
local.citation.epage16
local.citation.issue8
local.citation.spage1
local.description.resumoZika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-D-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration.
local.identifier.orcidhttps://orcid.org/0000-0002-0175-642X
local.identifier.orcidhttps://orcid.org/0000-0002-5682-3773
local.identifier.orcidhttps://orcid.org/0000-0002-7751-3061
local.identifier.orcidhttps://orcid.org/0000-0001-8876-3827
local.identifier.orcidhttps://orcid.org/0000-0002-2002-8436
local.identifier.orcidhttps://orcid.org/0000-0001-8835-8071
local.identifier.orcidhttps://orcid.org/0000-0002-9621-5422
local.identifier.orcidhttps://orcid.org/0000-0001-5297-9108
local.identifier.orcidhttps://orcid.org/0000-0003-3432-0769
local.identifier.orcidhttps://orcid.org/0000-0001-7042-9433
local.identifier.orcidhttps://orcid.org/0000-0002-6944-3008
local.identifier.orcidhttps://orcid.org/0000-0002-5678-4006
local.identifier.orcidhttps://orcid.org/0000-0002-0007-3280
local.identifier.orcidhttps://orcid.org/0000-0002-6949-0947
local.identifier.orcidhttps://orcid.org/0000-0001-7463-6368
local.identifier.orcidhttps://orcid.org/0000-0002-6561-8018
local.publisher.countryBrasil
local.publisher.departmentICB - DEPARTAMENTO DE MORFOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://journals.asm.org/doi/10.1128/mBio.00350-17

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