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Cathepsin K has been recently detected in brain parenchyma and it has been linked to neurobehavioral disorders such as schizophrenia. Thus, the study of the functions that cathepsin K fulfils in the brain becomes highly relevant.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Cathepsin K messenger RNA was detectable in all brain regions of wild type (WT) mice. At the protein level, cathepsin K was detected by immunofluorescence microscopy in vesicles of neuronal and non-neuronal cells throughout the mouse brain. The hippocampus of WT mice exhibited the highest levels of cathepsin K activity in fluorogenic assays, while the cortex, striatum, and cerebellum revealed significantly lower enzymatic activities. At the molecular level, the proteolytic network of cysteine cathepsins was disrupted in the brain of cathepsin K-deficient (<jats:italic>Ctsk<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>) animals. Specifically, cathepsin B and L protein and activity levels were altered, whereas cathepsin D remained largely unaffected. Cystatin C, an endogenous inhibitor of cysteine cathepsins, was elevated in the striatum and hippocampus, pointing to regional differences in the tissue response to <jats:italic>Ctsk<\/jats:italic> ablation. Decreased levels of astrocytic glial fibrillary acidic protein, fewer and less ramified profiles of astrocyte processes, differentially altered levels of oligodendrocytic cyclic nucleotide phosphodiesterase, as well as alterations in the patterning of neuronal cell layers were observed in the hippocampus of <jats:italic>Ctsk<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup> mice. A number of molecular and cellular changes were detected in other brain regions, including the cortex, striatum\/mesencephalon, and cerebellum. Moreover, an overall induction of the dopaminergic system was found in <jats:italic>Ctsk<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup> animals which exhibited reduced anxiety levels as well as short- and long-term memory impairments in behavioral assessments.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>We conclude that deletion of the <jats:italic>Ctsk<\/jats:italic> gene can lead to deregulation of related proteases, resulting in a wide range of molecular and cellular changes in the CNS with severe consequences for tissue homeostasis. We propose that cathepsin K activity has an important impact on the development and maintenance of the CNS in mice.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2202-12-74","type":"journal-article","created":{"date-parts":[[2011,7,28]],"date-time":"2011-07-28T06:23:20Z","timestamp":1311834200000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Cathepsin K deficiency in mice induces structural and metabolic changes in the central nervous system that are associated with learning and memory deficits"],"prefix":"10.1186","volume":"12","author":[{"given":"Stephanie","family":"Dauth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxandra F","family":"S\u00eerbulescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Jordans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Rehders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Avena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Oswald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Lerchl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Saftig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Brix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,7,27]]},"reference":[{"key":"2423_CR1","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.biochi.2007.07.024","volume":"90","author":"K Brix","year":"2008","unstructured":"Brix K, Dunkhorst A, Mayer K, Jordans S: Cysteine cathepsins: cellular roadmap to different functions. 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