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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

Activation of neuronal N-methyl-d-aspartate receptor plays a pivotal role in Japanese encephalitis virus-induced neuronal cell damage

Authors: Zheng Chen, Xugang Wang, Usama Ashraf, Bohan Zheng, Jing Ye, Dengyuan Zhou, Hao Zhang, Yunfeng Song, Huanchun Chen, Shuhong Zhao, Shengbo Cao

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Overstimulation of glutamate receptors, especially neuronal N-methyl-d-aspartate receptor (NMDAR), mediates excitatory neurotoxicity in multiple neurodegenerative diseases. However, the role of NMDAR in the regulation of Japanese encephalitis virus (JEV)-mediated neuropathogenesis remains undisclosed. The primary objective of this study was to understand the function of NMDAR to JEV-induced neuronal cell damage and inflammation in the central nervous system.

Methods

The effect of JEV-induced NMDAR activation on the progression of Japanese encephalitis was evaluated using the primary mouse neuron/glia cultures and a mouse model of JEV infection. A high-affinity NMDAR antagonist MK-801 was employed to block the activity of NMDAR both in vitro and in vivo. The subsequent impact of NMDAR blockade was assessed by examining the neuronal cell death, glutamate and inflammatory cytokine production, and JEV-induced mice mortality.

Results

JEV infection enhanced the activity of NMDAR which eventually led to increased neuronal cell damage. The data obtained from our in vitro and in vivo assays demonstrated that NMDAR blockade significantly abrogated the neuronal cell death and inflammatory response triggered by JEV infection. Moreover, administration of NMDAR antagonist protected the mice from JEV-induced lethality.

Conclusion

NMDAR plays an imperative role in regulating the JEV-induced neuronal cell damage and neuroinflammation. Thus, NMDAR targeting may constitute a captivating approach to rein in Japanese encephalitis.
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Metadata
Title
Activation of neuronal N-methyl-d-aspartate receptor plays a pivotal role in Japanese encephalitis virus-induced neuronal cell damage
Authors
Zheng Chen
Xugang Wang
Usama Ashraf
Bohan Zheng
Jing Ye
Dengyuan Zhou
Hao Zhang
Yunfeng Song
Huanchun Chen
Shuhong Zhao
Shengbo Cao
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1280-8

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