Increased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies

J Neuropathol Exp Neurol. 2000 Oct;59(10):866-71. doi: 10.1093/jnen/59.10.866.

Abstract

The levels of 2 arachidonic acid metabolites formed either by enzymatic activity of cyclooxygenase, i.e. prostaglandin E2 (PGE2), or by free radical-catalyzed peroxidation, i.e. F2-isoprostane 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), were measured in the CSF of subjects with sporadic and familial Creutzfeldt-Jakob disease (CJD) and in brain homogenates of scrapie-infected mice. The CSF levels of both metabolites were increased in sporadic CJD (n = 52) and familial CJD (n = 10) patients when compared with a group of patients with noninflammatory disorders. Similarly, PGE2 and 8-epi-PGF2alpha levels were higher in brain homogenates obtained from C57BL/6J mice infected with the ME7 scrapie strain than in brain homogenates from control animals. As PGE2 is 1 of the most abundant prostaglandins released during inflammation and 8-epi-PGF2alpha is a quantitative marker of lipid peroxidation, our results provide in vivo biochemical evidence for the occurrence of inflammation and oxidative stress in human and experimental transmissible spongiform encephalopathies (TSEs), a concept so far based mainly on histopathological and in vitro evidence. Interestingly, in sporadic CJD patients, high CSF levels of PGE2, but not 8-epi-PGF2alpha, correlated with short survival time, suggesting that the inflammatory response correlates with the clinical duration of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Brain / metabolism*
  • Creutzfeldt-Jakob Syndrome / metabolism*
  • Creutzfeldt-Jakob Syndrome / mortality
  • Cyclooxygenase 2
  • Dinoprost / analogs & derivatives*
  • Dinoprost / biosynthesis*
  • Dinoprostone / biosynthesis*
  • F2-Isoprostanes
  • Female
  • Humans
  • Isoenzymes / metabolism
  • Lipid Peroxidation / physiology
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Microglia / enzymology
  • Middle Aged
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Scrapie / metabolism*
  • Survival Analysis

Substances

  • F2-Isoprostanes
  • Isoenzymes
  • Membrane Proteins
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone