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000284090 037__ $$aDZNE-2026-00098
000284090 041__ $$aEnglish
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000284090 1001_ $$aCosta, Vivian V.$$b0
000284090 245__ $$aN -Methyl- d -Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection
000284090 260__ $$aWashington, DC$$bAmerican Society for Microbiology$$c2017
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000284090 520__ $$aZika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration.IMPORTANCE Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment.
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000284090 650_7 $$2Other$$aNMDA receptor
000284090 650_7 $$2Other$$aZika virus
000284090 650_7 $$2Other$$aintraocular pressure
000284090 650_7 $$2Other$$amemantine
000284090 650_7 $$2Other$$amicrogliosis
000284090 650_7 $$2Other$$amouse model
000284090 650_7 $$2Other$$aneuronal death
000284090 650_7 $$2NLM Chemicals$$aNeuroprotective Agents
000284090 650_7 $$2NLM Chemicals$$aReceptors, N-Methyl-D-Aspartate
000284090 650_2 $$2MeSH$$aAnimals
000284090 650_2 $$2MeSH$$aDisease Models, Animal
000284090 650_2 $$2MeSH$$aMice
000284090 650_2 $$2MeSH$$aNeurodegenerative Diseases: drug therapy
000284090 650_2 $$2MeSH$$aNeurodegenerative Diseases: pathology
000284090 650_2 $$2MeSH$$aNeuroprotective Agents: administration & dosage
000284090 650_2 $$2MeSH$$aReceptors, N-Methyl-D-Aspartate: antagonists & inhibitors
000284090 650_2 $$2MeSH$$aTreatment Outcome
000284090 650_2 $$2MeSH$$aZika Virus: growth & development
000284090 650_2 $$2MeSH$$aZika Virus Infection: complications
000284090 650_2 $$2MeSH$$aZika Virus Infection: pathology
000284090 7001_ $$aDel Sarto, Juliana L.$$b1
000284090 7001_ $$aRocha, Rebeca F.$$b2
000284090 7001_ $$aSilva, Flavia R.$$b3
000284090 7001_ $$aDoria, Juliana G.$$b4
000284090 7001_ $$aOlmo, Isabella G.$$b5
000284090 7001_ $$aMarques, Rafael E.$$b6
000284090 7001_ $$aQueiroz-Junior, Celso M.$$b7
000284090 7001_ $$aFoureaux, Giselle$$b8
000284090 7001_ $$aAraújo, Julia Maria S.$$b9
000284090 7001_ $$aCramer, Allysson$$b10
000284090 7001_ $$aReal, Ana Luíza C. V.$$b11
000284090 7001_ $$0P:(DE-2719)9001782$$aSecchim Ribeiro, Lucas$$b12$$udzne
000284090 7001_ $$aSardi, Silvia I.$$b13
000284090 7001_ $$aFerreira, Anderson J.$$b14
000284090 7001_ $$aMachado, Fabiana S.$$b15
000284090 7001_ $$ade Oliveira, Antônio C.$$b16
000284090 7001_ $$aTeixeira, Antônio L.$$b17
000284090 7001_ $$aNakaya, Helder I.$$b18
000284090 7001_ $$aSouza, Danielle G.$$b19
000284090 7001_ $$aRibeiro, Fabiola M.$$b20
000284090 7001_ $$aTeixeira, Mauro M.$$b21
000284090 773__ $$0PERI:(DE-600)2557172-2$$a10.1128/mBio.00350-17$$gVol. 8, no. 2, p. e00350-17$$n2$$pe00350-17$$tmBio$$v8$$x2161-2129$$y2017
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