{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:46:46Z","timestamp":1790196406739,"version":"4.1.0"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T00:00:00Z","timestamp":1493078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T00:00:00Z","timestamp":1493769600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"National Institute os Science and Technology in Dengue (INCT Dengue) a scheme funded by the Brazilian CNPq and FAPEMIG"},{"name":"Comiss\u00e3o de apoio a Pessoal de Ensino Superior"},{"name":"Financiadora de Estudos e Pesquisa"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2017,5,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by\n                    <jats:italic>N<\/jats:italic>\n                    -methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -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,\n                    <jats:italic>in vivo<\/jats:italic>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barr\u00e9 syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . 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.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00350-17","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T20:10:14Z","timestamp":1493151014000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":83,"title":["<i>N<\/i>\n                    -Methyl-\n                    <scp>d<\/scp>\n                    -Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection"],"prefix":"10.1128","volume":"8","author":[{"given":"Vivian V.","family":"Costa","sequence":"first","affiliation":[{"name":"Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil"},{"name":"Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana L.","family":"Del Sarto","sequence":"additional","affiliation":[{"name":"Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca F.","family":"Rocha","sequence":"additional","affiliation":[{"name":"Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia R.","family":"Silva","sequence":"additional","affiliation":[{"name":"Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana G.","family":"Doria","sequence":"additional","affiliation":[{"name":"Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella G.","family":"Olmo","sequence":"additional","affiliation":[{"name":"Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael E.","family":"Marques","sequence":"additional","affiliation":[{"name":"Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso M.","family":"Queiroz-Junior","sequence":"additional","affiliation":[{"name":"Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle","family":"Foureaux","sequence":"additional","affiliation":[{"name":"Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Maria S.","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allysson","family":"Cramer","sequence":"additional","affiliation":[{"name":"Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil"},{"name":"Immunoregulation of Infectious Disease Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Lu\u00edza C. 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