Differences in expression patterns of cathepsin <scp>C</scp>/dipeptidyl peptidase <scp>I</scp> in normal, pathological and aged mouse central nervous system

<jats:title>Abstract</jats:title><jats:p>Cathepsin <jats:styled-content style="fixed-case">C</jats:styled-content> (<jats:styled-content style="fixed-case">CC</jats:styled-content>) (<jats:styled-content style="fixed-case">EC</jats:styled-content> 3.4.14.1, dipeptidyl peptidase I) is a lysosomal cysteine protease that is required for the activation of several granule‐associated serine proteases <jats:italic>in vivo</jats:italic>. <jats:styled-content style="fixed-case">CC</jats:styled-content> has been shown to be constitutively expressed in various tissues, but the enzyme is hardly detectable in central nervous system (<jats:styled-content style="fixed-case">CNS</jats:styled-content>) tissues. In the present study, we investigated the regional and cellular distribution of <jats:styled-content style="fixed-case">CC</jats:styled-content> in normal, aging and pathological mouse brains. Immunoblotting failed to detect <jats:styled-content style="fixed-case">CC</jats:styled-content> protein in whole brain tissues of normal mice, as previously described. However, low proteolytic activity of <jats:styled-content style="fixed-case">CC</jats:styled-content> was detected in a brain region‐dependent manner, and granular immunohistochemical signals were found in neuronal perikarya of particular brain regions, including the accessory olfactory bulb, the septum, <jats:styled-content style="fixed-case">CA</jats:styled-content>2 of the hippocampus, a part of the cerebral cortex, the medial geniculate, and the inferior colliculus. In aged mice, the number of <jats:styled-content style="fixed-case">CC</jats:styled-content>‐positive neurons increased to some extent. The protein level of <jats:styled-content style="fixed-case">CC</jats:styled-content> and its proteolytic activity showed significant increases in particular brain regions of mouse models with pathological conditions – the thalamus in cathepsin <jats:styled-content style="fixed-case">D</jats:styled-content>‐deficient mice, the hippocampus of ipsilateral brain hemispheres after hypoxic–ischemic brain injury, and peri‐damaged portions of brains after penetrating injury. In such pathological conditions, the majority of the cells that were strongly immunopositive for <jats:styled-content style="fixed-case">CC</jats:styled-content> were activated microglia. These lines of evidence suggest that <jats:styled-content style="fixed-case">CC</jats:styled-content> is involved in normal neuronal function in certain brain regions, and also participates in inflammatory processes accompanying pathogenesis in the <jats:styled-content style="fixed-case">CNS</jats:styled-content>.</jats:p>