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Journal of Neuroscience, Vol 16, 2553-2562, Copyright © 1996 by Society for Neuroscience
Astrocytes protect neurons from hydrogen peroxide toxicity
S Desagher, J Glowinski and J Premont
Chaire de Neuropharmacologie, Institut National de la Sante et de la Recherche Medicale U114, College de France, Paris.
Recent reports indicate that neurons are particularly sensitive to hydrogen
peroxide (H2O2). The present study was undertaken to investigate the
putative role of astrocytes in the modulation of the neurotoxic effect of
H2O2. The exposure to H2O2 of cultured striatal neurons from mouse embryos
induced a concentration-dependent (10-1000 microM) cell death as estimated
24 hr later. Two methods were used to estimate neuronal survival: the
3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide assay or an
enzyme-linked immunosorbent assay with antibodies directed against an
antigen located in neurons (microtubule-associated protein-2). The
neurotoxic effect of H2O2 on neurons cocultured with astrocytes was
strongly attenuated compared with that observed on a pure population of
neurons seeded at the same density. Moreover, the protective effect of
astrocytes depended on the astrocytes/neurons ratio, a significant
neuroprotection being detectable for 1 astrocyte to 20 neurons. Catalase
seems to be the main hydrogen peroxidase activity involved in the
neuroprotective effect of astrocytes. Indeed, in the culture conditions
used, this enzymatic activity was enriched in this cell type compared with
neurons; its inhibition, and not that of glutathione peroxidase, reduced
the disappearance rate of the oxidant. On the contrary, glutathione
peroxidase appeared to be the main enzymatic activity involved in the
neuronal defense against H2O2 toxicity. Therefore, astrocytes could delay
neuronal death in pathological situations in which H2O2 has been, at least
partially, demonstrated to be involved.
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