Transient forebrain ischemia induces increased expression and specific localization of cathepsins E and D in rat...

The accumulation and localization of cathepsins E and D in the rat hippocampus and neostriatum during the neurodegenerating process induced by transient forebrain ischemia were investigated by immunoprecipitation and by immunohistochemistry using discriminative antibodies specific for each enzyme. While significant amounts of cathepsin D were found in both the hippocampus and the neostriatum of normal rats, cathepsin E was barely detectable in these tissues. No significant change in their levels was found in these tissues of postischemic rats for up to 3 days after transient forebrain ischemia. After 7 days of the treatment, cathepsin E was markedly increased in both tissues. Although the cathepsin D content in these tissues was also increased at this stage, the rate of increase was much less than that of cathepsin E. At the light microscopic level, the increased immunoreactivity for each enzyme was mainly found in reactive glial cells and degenerating neurons in the hippocampal CA1 subfield at 7 days postischemia. In the neostriatal dorsolateral portion, cathepsin D immunoreactivity was also increased in both reactive glial cells and degenerating neurons, whereas increased immunoreactivity of cathepsin E was only identified in reactive glial cells at 7 days postischemia. It was also found by double-immunostaining technique that the cathepsin E-positive glial cells were largely reactive microglial cells, whereas the cathepsin D-positive glial cells were associated mainly with reactive astrocytes. These results suggest that the accumulation of both cathepsins E and D in the regions of selective neuronal vulnerability may be associated with the postischemic development of intense gliosis and also probably neurodegenerative responses.