DISTRIBUTION OF MITOCHONDRIAL MANGANESE SUPEROXIDE-DISMUTASE AMONG RAT GLIAL-CELLS IN CULTURE

Enzymatic antioxidant defense systems, like superoxide dismutase (SOD) , mag protect neuronal and glial cells from reactive oxygen species (R OS) damage. Beside the cytosolic constitutive CuZn SOD, mitochondrial manganese SOD (Mn SOD) represents a ROS inducible enzyme which should allow the adaptation of brain cells to variation in ROS concentrations resulting from their oxidative metabolism. Using immunocytochemistry, the distribution of Mn SOD among the various representatives of the r at brain glial population (astroglia and microglia in primary culture as well as oligodendroglia in secondary culture) has been examined. Am ong astroglial cells, only a population of flat polygonal-shaped astro cytes, highly immunostained for glial fibrillary acid protein (GFAP) e xpress Mn SOD immunoreactivity. Microglial cells defined by their shap e and OX-42 immunoreactivity also express an intense Mn SOD signal. Ex posure of the primary culture to reactive oxygen species generated by a xanthine/xanthine oxidase mixture (X/XO) accentuates the Mn SOD sign al in astroglial and microglial cells. On the contrary, oligodendrogli al cells grown in secondary culture in a serum-free chemically defined or a serum-containing medium and well characterized by their 2',3'-cy clic nucleotide 3'-phosphodiesterase (CNPase) immunoreactivity never e xpress any immunostaining for Mn SOD, even in response to an extracell ular reactive oxygen species generating source like X/XO. Likewise, a population of A2B5-positive glial cells which may represent bipotentia l O-2A progenitor precursors does not express Mn SOD immunostaining. T hese results point out that in addition to the well known ability of m icroglial and astroglial cells to secrete ROS, they also express a hig h mitochondrial oxygen superoxide decomposition potential. On the cont rary the absence of any observable Mn SOD signal in precursors and in more differentiated oligodendroglial cells could be related to their g reat sensitivity to ROS damage and could therefore play an important r ole in the development of various dysmyelinating disorders. (C) 1998 W iley-Liss, Inc.