PMID- 28442607
OWN - NLM
STAT- MEDLINE
DCOM- 20180108
LR  - 20191227
IS  - 2150-7511 (Electronic)
VI  - 8
IP  - 2
DP  - 2017 Apr 25
TI  - N-Methyl-d-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by 
      Zika Virus Infection.
LID - 10.1128/mBio.00350-17 [doi]
LID - e00350-17
AB  - 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-Barre 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.
CI  - Copyright (c) 2017 Costa et al.
FAU - Costa, Vivian V
AU  - Costa VV
AD  - Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
AD  - Host-Interaction Microorganism Lab, Department of Microbiology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo 
      Horizonte, Minas Gerais, Brazil.
FAU - Del Sarto, Juliana L
AU  - Del Sarto JL
AD  - Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
FAU - Rocha, Rebeca F
AU  - Rocha RF
AD  - Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
FAU - Silva, Flavia R
AU  - Silva FR
AD  - Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
FAU - Doria, Juliana G
AU  - Doria JG
AD  - Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
FAU - Olmo, Isabella G
AU  - Olmo IG
AD  - Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
FAU - Marques, Rafael E
AU  - Marques RE
AD  - Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
FAU - Queiroz-Junior, Celso M
AU  - Queiroz-Junior CM
AD  - Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences 
      (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, 
      Brazil.
FAU - Foureaux, Giselle
AU  - Foureaux G
AD  - Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences 
      (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, 
      Brazil.
FAU - Araujo, Julia Maria S
AU  - Araujo JMS
AD  - Host-Interaction Microorganism Lab, Department of Microbiology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo 
      Horizonte, Minas Gerais, Brazil.
FAU - Cramer, Allysson
AU  - Cramer A
AD  - Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
AD  - Immunoregulation of Infectious Disease Lab, Department of Biochemistry and 
      Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas 
      Gerais (UFMG), Minas Gerais, Brazil.
FAU - Real, Ana Luiza C V
AU  - Real ALCV
AD  - Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
FAU - Ribeiro, Lucas S
AU  - Ribeiro LS
AD  - Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
AD  - Host-Interaction Microorganism Lab, Department of Microbiology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo 
      Horizonte, Minas Gerais, Brazil.
FAU - Sardi, Silvia I
AU  - Sardi SI
AD  - Virology Lab, Department of Virology, Universidade Federal da Bahia (UFBA), 
      Salvador, Bahia, Brazil.
FAU - Ferreira, Anderson J
AU  - Ferreira AJ
AD  - Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences 
      (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, 
      Brazil.
FAU - Machado, Fabiana S
AU  - Machado FS
AD  - Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
AD  - Immunoregulation of Infectious Disease Lab, Department of Biochemistry and 
      Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas 
      Gerais (UFMG), Minas Gerais, Brazil.
FAU - de Oliveira, Antonio C
AU  - de Oliveira AC
AD  - Neuropharmacology Lab, Department of Pharmacology, Institute of Biological 
      Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Teixeira, Antonio L
AU  - Teixeira AL
AD  - Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, 
      McGovern Medical Houston, University of Texas Health Science Center at Houston, 
      Houston, Texas, USA.
FAU - Nakaya, Helder I
AU  - Nakaya HI
AD  - Metabolomics Applied to Health Lab, Department of Clinical Analyses and 
      Toxicology, School of Pharmaceutical Science, Universidade de Sao Paulo (USP), 
      Sao Paulo, Brazil.
FAU - Souza, Danielle G
AU  - Souza DG
AD  - Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas 
      Gerais, Brazil.
AD  - Host-Interaction Microorganism Lab, Department of Microbiology, Institute of 
      Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo 
      Horizonte, Minas Gerais, Brazil.
FAU - Ribeiro, Fabiola M
AU  - Ribeiro FM
AD  - 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.
FAU - Teixeira, Mauro M
AU  - Teixeira MM
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170425
PL  - United States
TA  - mBio
JT  - mBio
JID - 101519231
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
CIN - mBio. 2017 Jun 27;8(3):. PMID: 28655823
MH  - Animals
MH  - Disease Models, Animal
MH  - Mice
MH  - Neurodegenerative Diseases/*drug therapy/*pathology
MH  - Neuroprotective Agents/*administration & dosage
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Treatment Outcome
MH  - Zika Virus/*growth & development
MH  - Zika Virus Infection/*complications/*pathology
PMC - PMC5405231
OTO - NOTNLM
OT  - NMDA receptor
OT  - Zika virus
OT  - intraocular pressure
OT  - memantine
OT  - microgliosis
OT  - mouse model
OT  - neuronal death
EDAT- 2017/04/27 06:00
MHDA- 2018/01/09 06:00
PMCR- 2017/04/25
CRDT- 2017/04/27 06:00
PHST- 2017/04/27 06:00 [entrez]
PHST- 2017/04/27 06:00 [pubmed]
PHST- 2018/01/09 06:00 [medline]
PHST- 2017/04/25 00:00 [pmc-release]
AID - mBio.00350-17 [pii]
AID - mBio00350-17 [pii]
AID - 10.1128/mBio.00350-17 [doi]
PST - epublish
SO  - mBio. 2017 Apr 25;8(2):e00350-17. doi: 10.1128/mBio.00350-17.