Oxidative damage to neurons caused by the induction of microglial NADPH oxidase in encephalomyocarditis virus infection.
Reactive oxygen species (ROS) play an important role in diverse vital functions including host defense via anti-viral and anti-bacterial effects, but ROS also lead to peroxynitrite and hydroxyl radical production, which are powerful mediators of brain injury in brain inflammation. It is known that NADPH oxidases (NOX) are the major source of ROS. In the present study, NOX2 expression and distribution were examined after intracranial encephalomyocarditis virus B variant (EMCV-B) infection, which causes encephalitis. The reverse transcriptase (RT)-polymerase chain reaction (PCR) and immunohistochemistry showed that the expression and distribution of NOX2 were significantly up-regulated after EMCV-B infection in microglial cells, which invaded into the surrounding regions where neurons were subjected to oxidative stress. These findings suggest that the oxidative stress generated by NOX2 in activated microglial cells damages neurons and that this is an important process in the pathogenesis of EMCV-B infection.
Ano
Yasuhisa
Y
Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Sakudo
Akikazu
A
Kimata
Tetsuya
T
Uraki
Ryuta
R
Sugiura
Katsuaki
K
Onodera
Takashi
T
D000818:Animals; D001921:Brain / Q000378:metabolism*; D018188:Cardiovirus Infections / Q000378:metabolism*; D004686:Encephalomyocarditis virus / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D007739:L Cells; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D017628:Microglia / Q000201:enzymology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014779:Virus Replication
D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases