ASTROCYTES AND CATALASE PREVENT THE TOXICITY OF CATECHOLAMINES TO OLIGODENDROCYTES

Metabolism of catecholamines can generate reactive free radical specie s, 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 concent rations of H2O2, could be completely prevented by simultaneous treatme nt of OLs with the H2O2-decomposing enzyme catalase. These results imp licate H2O2 produced by metabolism of NE and EPI as the toxic intermed iate. Since OLs in vivo are not normally susceptible to the toxicity o f catecholamine neurotransmitter molecules, we sought to examine the i nvolvement of another cell type closely apposed to OL, that is astrocy tes, as a protectant against catecholamine toxicity. When adult rat OL s were seeded onto a monolayer of neonatal rat astrocytes, the toxicit y of NE, EPI and H2O2 to OLs was completely prevented; medium conditio ned by astrocytes did not prevent the manifestation of H2O2 toxicity o n OLs. We conclude that the OL-myelin complex is vulnerable to free ra dical-mediated damage, especially when the protective functions of ast rocytes are impaired.