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

• Autor(a) principal: Vivian Vasconcelos Costa
• Data de Publicação: 2017
• Outros Autores: Julia Maria S. Araújo, Allysson Cramer, Ana Luíza Campos Vila Real, Lucas Secchim Ribeiro, Silvia Ines Sardi, Anderson J. Ferreira, Fabiana Simão Machado, Antônio Costa de Oliveira, Antônio Lúcio Teixeira, Helder Nakaya, Danielle da Glória de Souza, Fabiola M. Ribeiro, Mauro Martins Teixeira, Rebeca de Paiva Froes Rocha, Flavia R. Silva, Juliana G. Doria, Isabella Guimarães Olmo, Rafael Elias Marques Pereira Silva, Celso Martins Queiroz Junior, Giselle Foureaux, Juliana Lemos Del Sarto
• Tipo de documento: Artigo de conferência
• Idioma: por
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: https://doi.org/10.1128/mbio.00350-17; http://hdl.handle.net/1843/56300; https://orcid.org/0000-0002-0175-642X; https://orcid.org/0000-0002-5682-3773; https://orcid.org/0000-0002-7751-3061; https://orcid.org/0000-0001-8876-3827; https://orcid.org/0000-0002-2002-8436; https://orcid.org/0000-0001-8835-8071; https://orcid.org/0000-0002-9621-5422; https://orcid.org/0000-0001-5297-9108; https://orcid.org/0000-0003-3432-0769; https://orcid.org/0000-0001-7042-9433; https://orcid.org/0000-0002-6944-3008; https://orcid.org/0000-0002-5678-4006; https://orcid.org/0000-0002-0007-3280; https://orcid.org/0000-0002-6949-0947; https://orcid.org/0000-0001-7463-6368; https://orcid.org/0000-0002-6561-8018
• topic: NMDA receptor; Zika virus; Intraocular pressure; Memantine; Microgliosis; Mouse model; Neuronal death; Medicina; Microbiologia; Pressão intra-ocular

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.