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@ARTICLE{Costa:284090,
author = {Costa, Vivian V. and Del Sarto, Juliana L. and Rocha,
Rebeca F. and Silva, Flavia R. and Doria, Juliana G. and
Olmo, Isabella G. and Marques, Rafael E. and Queiroz-Junior,
Celso M. and Foureaux, Giselle and Araújo, Julia Maria S.
and Cramer, Allysson and Real, Ana Luíza C. V. and Secchim
Ribeiro, Lucas and Sardi, Silvia I. and Ferreira, Anderson
J. and Machado, Fabiana S. and de Oliveira, Antônio C. and
Teixeira, Antônio L. and Nakaya, Helder I. and Souza,
Danielle G. and Ribeiro, Fabiola M. and Teixeira, Mauro M.},
title = {{N} -{M}ethyl- d -{A}spartate ({NMDA}) {R}eceptor
{B}lockade {P}revents {N}euronal {D}eath {I}nduced by {Z}ika
{V}irus {I}nfection},
journal = {mBio},
volume = {8},
number = {2},
issn = {2161-2129},
address = {Washington, DC},
publisher = {American Society for Microbiology},
reportid = {DZNE-2026-00098},
pages = {e00350-17},
year = {2017},
abstract = {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.},
keywords = {Animals / Disease Models, Animal / Mice / Neurodegenerative
Diseases: drug therapy / Neurodegenerative Diseases:
pathology / Neuroprotective Agents: administration $\&$
dosage / Receptors, N-Methyl-D-Aspartate: antagonists $\&$
inhibitors / Treatment Outcome / Zika Virus: growth $\&$
development / Zika Virus Infection: complications / Zika
Virus Infection: pathology / NMDA receptor (Other) / Zika
virus (Other) / intraocular pressure (Other) / memantine
(Other) / microgliosis (Other) / mouse model (Other) /
neuronal death (Other) / Neuroprotective Agents (NLM
Chemicals) / Receptors, N-Methyl-D-Aspartate (NLM
Chemicals)},
ddc = {570},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
doi = {10.1128/mBio.00350-17},
url = {https://pub.dzne.de/record/284090},
}