Neurochemical Research

, Volume 32, Issue 2, pp 279–292 | Cite as

The Neurotoxic Effect of Cuprizone on Oligodendrocytes Depends on the Presence of Pro-inflammatory Cytokines Secreted by Microglia

  • L. A. Pasquini
  • C. A. Calatayud
  • A. L. Bertone Uña
  • V. Millet
  • J. M. Pasquini
  • E. F. Soto
Original paper


In order to further characterize the still unknown mechanism of cuprizone-induced demyelination, we investigated its effect on rat primary oligodendroglial cell cultures. Cell viability was not significantly affected by this treatment. However, when concentrations of IFNγ and/or TNFα having no deleterious effects per se on cell viability were added together with cuprizone, cell viability decreased significantly. In mitochondria isolated from cuprizone-treated glial cells, we observed a marked decrease in the activities of the various complexes of the respiratory chain, indicating a disruption of mitochondrial function. An enhancement in oxidant production was also observed in cuprizone and/or TNFα-treated oligodendroglial cells. In in vivo experiments, inhibition of microglial activation with minocycline prevented cuprizone-induced demyelination. Based on the above-mentioned results we suggest that these microglial cells appear to have a very active role in cuprizone-induced oligodendroglial cell death and demyelination, through the production and secretion of pro-inflammatory cytokines.


Cuprizone Cytokines Oligodendrocytes Myelin Demyelination Microglia 



Contract grant sponsor: Universidad de Buenos Aires B114 and Agencia Nacional de Promoción de Ciencia y Tecnología (PICT 12282). The authors wish to express their gratitude to Dra. Laura Pardo from FUNDALEU, for her help with the flow cytometry data.


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • L. A. Pasquini
    • 1
  • C. A. Calatayud
    • 1
  • A. L. Bertone Uña
    • 1
  • V. Millet
    • 1
  • J. M. Pasquini
    • 1
  • E. F. Soto
    • 1
  1. 1.Departamento de Química Biológica, Facultad de Farmacia y BioquímicaUniversidad de Buenos AiresBuenos AiresArgentina

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