INVESTIGADORES
PASQUINI juana Maria
artículos
Título:
The neurotoxic effect of cuprizone on oligodendrocytes depends on the presence of pro-inflammatory cytokines secreted by microglia
Autor/es:
PASQUINI LA, CALATAYUD CA, BERTONE UÑA AL, MILLET V, PASQUINI JM, SOTO EF.
Revista:
NEUROCHEMICAL RESEARCH
Editorial:
Springer-Link
Referencias:
Lugar: Nueva York; Año: 2007 vol. 32 p. 279 - 292
ISSN:
0364-3190
Resumen:
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 IFNgamma and/or TNFalpha 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 TNFalpha-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.