ELEVATED CATHEPSIN-D EXPRESSION IN KAINATE-EVOKED RAT-BRAIN NEURODEGENERATION

Expression patterns of cathepsin D (lysosomal aspartic protease) and g lial fibrillary acidic protein (GFAP, a marker of reactive astroglia) were determined by Northern blot analysis and immunohistochemistry in the rat brain during neurodegeneration accompanying kainate-evoked sei zures. The level of cathepsin D mRNA in the hippocampus, limbic cortex , and temporo-parieto-occipital neocortex was shown to increase, start ing at 6 h after kainate treatment, and reaching peak values at 3-7 da ys after the neurotoxin administration. A similar time course of eleva ted accumulation was noted for GFAP mRNA in these structures. Immunohi stochemical analysis performed 3 days after kainate treatment showed t hat the increased cathepsin D levels were confined mainly to the degen erating neurons in the susceptible brain areas, while the elevated GFA P immunoreactivity was observed in reactive astrocytes. Although cathe psin D and GFAP expression levels were elevated by kainate administrat ion, their expression patterns revealed significant differences with r egard to both intensity and site of induction. (C) 1995 Academic Press , Inc.