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

Autor:	Costa VV; Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.; Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Del Sarto JL; Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Rocha RF; Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Silva FR; Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Doria JG; Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Olmo IG; Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Marques RE; Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Queiroz-Junior CM; Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Foureaux G; Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Araújo JMS; Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Cramer A; Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.; Immunoregulation of Infectious Disease Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Real ALCV; Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Ribeiro LS; Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.; Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Sardi SI; Virology Lab, Department of Virology, Universidade Federal da Bahia (UFBA), Salvador, Bahia, Brazil., Ferreira AJ; Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Machado FS; Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.; Immunoregulation of Infectious Disease Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., de Oliveira AC; Neuropharmacology Lab, Department of Pharmacology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Teixeira AL; Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical Houston, University of Texas Health Science Center at Houston, Houston, Texas, USA., Nakaya HI; Metabolomics Applied to Health Lab, Department of Clinical Analyses and Toxicology, School of Pharmaceutical Science, Universidade de Sao Paulo (USP), Sao Paulo, Brazil., Souza DG; Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.; Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Ribeiro FM; Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil fmribeiro@icb.ufmg.br mmtex.ufmg@gmail.com., Teixeira MM; Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil fmribeiro@icb.ufmg.br mmtex.ufmg@gmail.com.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2017 Apr 25; Vol. 8 (2). Date of Electronic Publication: 2017 Apr 25.
DOI:	10.1128/mBio.00350-17
Abstrakt:	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. 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. (Copyright © 2017 Costa et al.)
Databáze:	MEDLINE
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