Upregulation of COX-2 and CGRP expression in resident cells of the Borna disease virus-infected brain is dependent upon inflammation

Neurobiol Dis. 1999 Feb;6(1):15-34. doi: 10.1006/nbdi.1998.0225.

Abstract

Infection of immunocompetent adult rats with Borna disease virus (BDV) causes severe encephalitis and neural dysfunction. The expression of COX-2 and CGRP, genes previously shown to be implicated in CNS disease and peripheral inflammation, was dramatically upregulated in the cortical neurons of acutely BDV-infected rats. Neuronal COX-2 and CGRP upregulation was predominantly seen in brain areas where ED1-positive macrophages/microglia accumulated. In addition, COX-2 expression was strongly induced in brain endothelial cells and the number of COX-2 immunoreactive microglial cells was increased. In contrast, despite increased expression of viral antigens, neither COX-2 nor CGRP expression was altered in the CNS of BDV-infected rats treated with dexamethasone, or tolerant to BDV. Thus, increased CGRP and COX-2 expression in the BDV-infected brain is the result of the inflammatory response and likely to be involved in the pathogenesis of virus-induced encephalitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antigens, Viral / analysis
  • Borna Disease / enzymology*
  • Borna Disease / immunology*
  • Brain Diseases / metabolism
  • Brain Diseases / virology
  • Calcitonin Gene-Related Peptide / analysis
  • Calcitonin Gene-Related Peptide / genetics*
  • Cyclooxygenase 2
  • Dexamethasone / pharmacology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / virology
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Enzymologic
  • Hippocampus / enzymology
  • Hippocampus / virology
  • Isoenzymes / analysis
  • Isoenzymes / genetics*
  • Macrophages / virology
  • Microglia / virology
  • Neocortex / enzymology
  • Neocortex / virology
  • Peroxidases / analysis
  • Peroxidases / genetics
  • Prostaglandin-Endoperoxide Synthases / analysis
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandins / immunology
  • Rats
  • Rats, Inbred Lew

Substances

  • Anti-Inflammatory Agents
  • Antigens, Viral
  • Isoenzymes
  • Prostaglandins
  • Dexamethasone
  • Peroxidases
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Calcitonin Gene-Related Peptide