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

Expression patterns of cathepsin D (lysosomal aspartic protease) and glial 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 seizures. The level of cathepsin D mRNA in the hippocampus, limbic cortex, and temporo-parieto-occipital neocortex was shown to increase, starting at 6 h after kainate treatment, and reaching peak values at 3-7 days after the neurotoxin administration. A similar time course of elevated accumulation was noted for GFAP mRNA in these structures. Immunohistochemical analysis performed 3 days after kainate treatment showed that the increased cathepsin D levels were confined mainly to the degenerating neurons in the susceptible brain areas, while the elevated GFAP immunoreactivity was observed in reactive astrocytes. Although cathepsin D and GFAP expression levels were elevated by kainate administration, their expression patterns revealed significant differences with regard to both intensity and site of induction. (C) 1995 Academic Press, Inc.