Abrogated inflammatory response promotes neurogenesis in a murine model of Japanese encephalitis

Sulagna Das, Kallol Dutta, Kanhaiya Lal Kumawat, Ayan Ghoshal, Dwaipayan Adhya, Anirban Basu

Research output: Contribution to journalArticle

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Abstract

Background: Japanese encephalitis virus (JEV) induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline. Methodology/Principal Findings: Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE) and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used. Conclusion/Significance: This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors.

Original languageEnglish (US)
Article numbere17225
JournalPloS one
Volume6
Issue number3
DOIs
StatePublished - Mar 10 2011
Externally publishedYes

Fingerprint

Japanese Encephalitis Virus
minocycline
Japanese Encephalitis
Japanese encephalitis virus
Minocycline
neurogenesis
Neurogenesis
encephalitis
Viruses
neuroglia
Microglia
inflammation
animal models
Conditioned Culture Medium
Inflammation
niches
Anti-Inflammatory Agents
viral encephalitis
Viral Encephalitis
complications (disease)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Abrogated inflammatory response promotes neurogenesis in a murine model of Japanese encephalitis. / Das, Sulagna; Dutta, Kallol; Kumawat, Kanhaiya Lal; Ghoshal, Ayan; Adhya, Dwaipayan; Basu, Anirban.

In: PloS one, Vol. 6, No. 3, e17225, 10.03.2011.

Research output: Contribution to journalArticle

Das, Sulagna ; Dutta, Kallol ; Kumawat, Kanhaiya Lal ; Ghoshal, Ayan ; Adhya, Dwaipayan ; Basu, Anirban. / Abrogated inflammatory response promotes neurogenesis in a murine model of Japanese encephalitis. In: PloS one. 2011 ; Vol. 6, No. 3.
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