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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Immunol
2017 ; 8
(ä): 1016
Nephropedia Template TP
gab.com Text
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English Wikipedia
Zika Virus Promotes Neuronal Cell Death in a Non-Cell Autonomous Manner by
Triggering the Release of Neurotoxic Factors
#MMPMID28878777
Olmo IG
; Carvalho TG
; Costa VV
; Alves-Silva J
; Ferrari CZ
; Izidoro-Toledo TC
; da Silva JF
; Teixeira AL
; Souza DG
; Marques JT
; Teixeira MM
; Vieira LB
; Ribeiro FM
Front Immunol
2017[]; 8
(ä): 1016
PMID28878777
show ga
Zika virus (ZIKV) has recently caused a worldwide outbreak of infections
associated with severe neurological complications, including microcephaly in
infants born from infected mothers. ZIKV exhibits high neurotropism and promotes
neuroinflammation and neuronal cell death. We have recently demonstrated that
N-methyl-d-aspartate receptor (NMDAR) blockade by memantine prevents ZIKV-induced
neuronal cell death. Here, we show that ZIKV induces apoptosis in a non-cell
autonomous manner, triggering cell death of uninfected neurons by releasing
cytotoxic factors. Neuronal cultures infected with ZIKV exhibit increased levels
of tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and glutamate.
Moreover, infected neurons exhibit increased expression of GluN2B and augmented
intracellular Ca(2+) concentration. Blockade of GluN2B-containing NMDAR by
ifenprodil normalizes Ca(2+) levels and rescues neuronal cell death. Notably,
TNF-? and IL-1? blockade decreases ZIKV-induced Ca(2+) flux through
GluN2B-containing NMDARs and reduces neuronal cell death, indicating that these
cytokines might contribute to NMDAR sensitization and neurotoxicity. In addition,
ZIKV-infected cultures treated with ifenprodil exhibits increased activation of
the neuroprotective pathway including extracellular signal-regulated kinase and
cAMP response element-binding protein, which may underlie ifenprodil-mediated
neuroprotection. Together, our data shed some light on the neurotoxic mechanisms
triggered by ZIKV and begin to elucidate how GluN2B-containing NMDAR blockade can
prevent neurotoxicity.