{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:42:48Z","timestamp":1789188168968,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,11,4]],"date-time":"2005-11-04T00:00:00Z","timestamp":1131062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2005,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Niemann\u2010Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is thought to result from deficient intracellular cholesterol and\/or ganglioside trafficking. We have investigated the effects of allopregnanolone treatments on survival, weight loss, motor function, magnetic resonance imaging (MRI), and neuropathology in the mouse model of NPC (<jats:italic>Npc1<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup> mice). We confirmed previous results showing that a single injection of 250 \u03bcg of allopregnanolone on postnatal day 7 significantly extended the life span of <jats:italic>Npc1<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup> mice. This caused a marked difference in the weight curves of the treated mice but no statistical difference in the Rota\u2010Rod performance. T2\u2010weighted MRI and diffusion tensor imaging (DTI) of treated mice showed values of signal intensity and fractional anisotropy closer to those of wild\u2010type mice than those of untreated <jats:italic>Npc1<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup> mice. Neuropathology showed that day\u20107 treatment markedly suppressed astrocyte reaction and significantly reduced microglial activation. Furthermore, the steroid treatment also increased myelination in brains of <jats:italic>Npc1<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup> mice. Similar effects of allopregnanolone treatment were observed in <jats:italic>Npc1<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup>, <jats:italic>mdr1a<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup> double\u2010mutant mice, which have a deficient blood\u2013brain barrier, resulting in increased steroid uptake. The effects on survival and weight loss of a single injection on day 7 followed by injections every 2 weeks were also evaluated in <jats:italic>Npc1<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup> mice, and the beneficial effects were found to be greater than with the single injection at day 7. We conclude that allopregnanolone treatment significantly ameliorates several symptoms of NPC in <jats:italic>Npc1<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup> mice, presumably by effects on myelination or neuronal connectivity. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.20685","type":"journal-article","created":{"date-parts":[[2005,11,16]],"date-time":"2005-11-16T16:17:33Z","timestamp":1132157853000},"page":"811-821","source":"Crossref","is-referenced-by-count":70,"title":["Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of Niemann\u2010Pick C 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