{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:58:52Z","timestamp":1779364732433,"version":"3.53.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,11,17]],"date-time":"2014-11-17T00:00:00Z","timestamp":1416182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>iemann\u2010<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>ick type <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>) disease is a fatal hereditary lysosomal lipid storage disease caused by mutations in <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>1 or <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>2. It is still unknown how this disorder evokes clinical signs. Typically, patients develop severe cerebellar ataxia due to progressive <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>urkinje cell loss. Hitherto, <jats:italic>in vitro<\/jats:italic> studies did not allow monitoring the natural process of <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>\u2010associated <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>urkinje cell degeneration. Aim of this study was to evaluate whether organotypic slice cultures are usable to monitor the natural process of <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>\u2010associated <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>urkinje\u2010cell degeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used organotypic cerebellar slice cultures of a well\u2010established <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> mouse model to display the natural history of cerebellar degeneration <jats:italic>in vitro<\/jats:italic> and cultivated them for a prolonged time period of 6 weeks for the first time. Moreover we tested several therapeutic candidates and evaluated their effect on <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>urkinje\u2010cell survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our approach proves that it is possible to monitor and to prevent <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>\u2010related <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>urkinje cell death reliably <jats:italic>in vitro<\/jats:italic>. This is beneficial because <jats:italic>in vivo<\/jats:italic>\u2005<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>urkinje cell loss directly translates into clinical signs. Thus, therapeutically interesting compounds can be tested <jats:italic>in vitro<\/jats:italic>, not only to correct biochemical abnormalities, but also to show the likelihood of a compound to prevent ataxia. As to be expected from the results of previous animal experiments, 2\u2010hydroxypropyl\u2010\u03b2\u2010cyclodextrin rescued <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>urkinje cells. We also discovered that 3\u2010methyladenine preserved <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>urkinje cell numbers by adjusting the autophagic flux in <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> slices.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We provide evidence that cerebellar slice cultures are a powerful <jats:italic>in vitro<\/jats:italic> tool to study <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>\u2010associated <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>urkinje cell death in an organotypic setting.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12154","type":"journal-article","created":{"date-parts":[[2014,5,30]],"date-time":"2014-05-30T07:15:19Z","timestamp":1401434119000},"page":"933-945","source":"Crossref","is-referenced-by-count":9,"title":["The natural history of cerebellar degeneration of <scp>N<\/scp>iemann\u2010<scp>P<\/scp>ick <scp>C<\/scp> 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