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Tipo:	Artigo de Periódico
Título:	N-Methyl-d-Aspartate (NMDA) receptor blockade prevents neuronal death induced by Zika Virus infection
Autor(es):	Vivian V. Costa Juliana L. Del Sarto Rebeca F. Rocha Flavia R. Silva Juliana G. Doria Isabella G. Olmo Rafael E. Marques Celso M. Queiroz Junior Giselle Foureaux Julia Maria S. Araújo Allysson Cramer Ana Luíza C. V. Real Lucas S. Ribeiro Silvia I. Sardi Anderson J. Ferreira Fabiana S. Machado Antônio C. de Oliveira Antônio L. Teixeira Helder I. Nakaya Danielle G. Souza Fabiola M. Ribeiro Mauro M. Teixeira
Resumo:	Zika 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.
Assunto:	Vírus da Zika Morte cerebral
Idioma:	eng
País:	Brasil
Editor:	Universidade Federal de Minas Gerais
Sigla da Instituição:	UFMG
Departamento:	ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA ICB - DEPARTAMENTO DE FARMACOLOGIA ICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA ICB - DEPARTAMENTO DE MICROBIOLOGIA ICB - DEPARTAMENTO DE MORFOLOGIA MED - DEPARTAMENTO DE CLÍNICA MÉDICA
Tipo de Acesso:	Acesso Aberto
Identificador DOI:	https://doi.org/10.1128/mbio.00350-17
URI:	http://hdl.handle.net/1843/79350
Data do documento:	3-Mai-2017
metadata.dc.url.externa:	https://journals.asm.org/doi/epdf/10.1128/mbio.00350-17
metadata.dc.relation.ispartof:	mBio
Aparece nas coleções:	Artigo de Periódico

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