Atorvastatin ameliorates viral burden and neural stem/ progenitor cell (NSPC) death in an experimental model of Japanese encephalitis
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Date
2020-06
Journal Title
Journal ISSN
Volume Title
Publisher
Indian Academy of Sciences
Abstract
Japanese encephalitis virus, a neurotropic flavivirus, causes sporadic encephalitis with nearly 25% fatal casereports. JEV infects neural stem/progenitor cells (NSPCs) and decreases their proliferation. Statin, a commonlyused class of cholesterol lowering drug, has been shown to possess potent anti-inflammatory and neuroprotective effects in acute brain injury and chronic neurodegenerative conditions. Here, we aimed to check theefficacy of atorvastatin in alleviating the symptoms of Japanese encephalitis (JE). Using BALB/c mouse modelof JEV infection, we observed that atorvastatin effectively reduces viral load in the subventricular zone (SVZ)of infected pups and decreases the resultant cell death. Furthermore, atorvastatin abrogates microglial activation and production of proinflammatory cyto/chemokine production post JEV infection in vivo. It alsoreduced interferon-b response in the neurogenic environs. The neuroprotective role of atorvastatin is againevident from the rescued neurosphere size and decreased cell death in vitro. It has also been observed that uponatorvastatin administration, cell cycle regulatory proteins and cell survival proteins are also restored to theirrespective expression level as observed in uninfected animals. Thus the antiviral, immunomodulatory andneuroprotective roles of atorvastatin reflect in our experimental observations. Therefore, this drug broadens apath for future therapeutic measures against JEV infection.
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Keywords
Atorvastatin, drug repurposing, Japanese encephalitis virus, neural stem/progenitor cell, neurotropic viruses, statins
Citation
Wani Masood Ahmad, Mukherjee Sriparna, Mallick Suvadip, Akbar Irshad, Basu Anirban. Atorvastatin ameliorates viral burden and neural stem/ progenitor cell (NSPC) death in an experimental model of Japanese encephalitis. Journal of Biosciences. 2020 Jun; : 1-17