Enhanced cellular glutathione peroxidase immunoreactivity in activated astrocytes and in microglia during excitotoxin induced neurodegeneration

The cellular distribution pattern of cellular glutathione peroxidase (GPx) was analyzed immunocytochemically in the normal rat central nervous system (CNS) and following exposure to the excitotoxin quinolinic acid (Quin). In the normal CNS, GPx was localized predominantly to microglia, identified by staining with isolectin B4 or the monoclonal antibody OX-42. Three days after intrastriatal administration of 90 pmoles Quin, GPx immunoreactivity was increased in activated microglia and also in astrocytes costained for glial fibrillary acidic protein (GFAP). Whereas GPx-positive astrocytes were seen predominantly in the environment of the lesion, most intensive immunoreactivity was located in globular-shaped microglia in the lesion core. GPx staining was generally low in neurons and failed to increase its intensity after lesion. In the case of excitotoxin-induced generation of oxygen-derived free radicals, the elevation of GPx levels in microglia, and likewise in activated astroglia, may provide an important mechanism to withstand oxidative stress.