Distribution of mitochondrial manganese superoxide dismutase among rat glial cells in culture.

Enzymatic antioxidant defense systems, like superoxide dismutase (SOD), may protect neuronal and glial cells from reactive oxygen species (ROS) 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 rat brain glial population (astroglia and microglia in primary culture as well as oligodendroglia in secondary culture) has been examined. Among astroglial cells, only a population of flat polygonal-shaped astrocytes, highly immunostained for glial fibrillary acid protein (GFAP) express Mn SOD immunoreactivity. Microglial cells defined by their shape and OX-42 immunoreactivity also express an intense Mn SOD signal. Exposure of the primary culture to reactive oxygen species generated by a xanthine/xanthine oxidase mixture (X/XO) accentuates the Mn SOD signal in astroglial and microglial cells. On the contrary, oligodendroglial cells grown in secondary culture in a serum-free chemically defined or a serum-containing medium and well characterized by their 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) immunoreactivity never express any immunostaining for Mn SOD, even in response to an extracellular reactive oxygen species generating source like X/XO. Likewise, a population of A2B5-positive glial cells which may represent bipotential O-2A progenitor precursors does not express Mn SOD immunostaining. These results point out that in addition to the well known ability of microglial and astroglial cells to secrete ROS, they also express a high mitochondrial oxygen superoxide decomposition potential. On the contrary, the absence of any observable Mn SOD signal in precursors and in more differentiated oligodendroglial cells could be related to their great sensitivity to ROS damage and could therefore play an important role in the development of various dysmyelinating disorders.