Astrocytes and catalase prevent the toxicity of catecholamines to oligodendrocytes

Metabolism of catecholamines can generate reactive free radical species, including hydrogen peroxide (H2O2), that are potentially harmful to cells. In this study, norepinephrine (NE) and epinephrine (EPI) were found to be toxic to oligodendrocyte (OL) cultures derived from adult rat brain. The catecholamine toxicity, reproduced by equimolar concentrations of H2O2, could be completely prevented by simultaneous treatment of OLs with the H2O2-decomposing enzyme catalase. These results implicate H2O2 produced by metabolism of NE and EPI as the toxic intermediate. Since OLs in vivo are not normally susceptible to the toxicity of catecholamine neurotransmitter molecules, we sought to examine the involvement of another cell type closely apposed to OL, that is astrocytes, as a protectant against catecholamine toxicity. When adult rat OLs were seeded onto a monolayer of neonatal rat astrocytes, the toxicity of NE, EPI and H2O2 to OLs was completely prevented; medium conditioned by astrocytes did not prevent the manifestation of H2O2 toxicity on OLs. We conclude that the OL-myelin complex is vulnerable to free radical-mediated damage, especially when the protective functions of astrocytes are impaired.