{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:36:05Z","timestamp":1790948165070,"version":"4.1.0"},"reference-count":161,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centre of Transdisciplinary Neuroscience Rostock","award":["Support"],"award-info":[{"award-number":["Support"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In a mouse model of Niemann-Pick disease type C1 (NPC1), a combination therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-\u03b2-cyclodextrin (HP\u00dfCD) has previously resulted in, among other things, significantly improved motor function. The present study was designed to compare the therapeutic effects of the COMBI therapy with that of MIGLU or HP\u00dfCD alone on body and brain weight and the behavior of NPC1\u2212\/\u2212 mice in a larger cohort, with special reference to gender differences. A total of 117 NPC1\u2212\/\u2212 and 123 NPC1+\/+ mice underwent either COMBI, MIGLU only, HP\u00dfCD only, or vehicle treatment (Sham), or received no treatment at all (None). In male and female NPC1\u2212\/\u2212 mice, all treatments led to decreased loss of body weight and, partly, brain weight. Concerning motor coordination, as revealed by the accelerod test, male NPC1\u2212\/\u2212 mice benefited from COMBI treatment, whereas female mice benefited from COMBI, MIGLU, and HP\u00dfCD treatment. As seen in the open field test, the reduced locomotor activity of male and female NPC1\u2212\/\u2212 mice was not significantly ameliorated in either treatment group. Our results suggest that in NPC1\u2212\/\u2212 mice, each drug treatment scheme had a beneficial effect on at least some of the parameters evaluated compared with Sham-treated mice. Only in COMBI-treated male and female NPC+\/+ mice were drug effects seen in reduced body and brain weights. Upon COMBI treatment, the increased dosage of drugs necessary for anesthesia in Sham-treated male and female NPC1\u2212\/\u2212 mice was almost completely reduced only in the female groups.<\/jats:p>","DOI":"10.3390\/ijms22052539","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T20:29:48Z","timestamp":1614803388000},"page":"2539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Gender-Specific Effects of Two Treatment Strategies in a Mouse Model of Niemann-Pick Disease Type C1"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-9093","authenticated-orcid":false,"given":"Carsten","family":"Holzmann","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics, Rostock University Medical Center, D-18057 Rostock, Germany"},{"name":"Centre of Transdisciplinary Neuroscience Rostock, D-18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4538-877X","authenticated-orcid":false,"given":"Martin","family":"Witt","sequence":"additional","affiliation":[{"name":"Centre of Transdisciplinary Neuroscience Rostock, D-18147 Rostock, Germany"},{"name":"Institute of Anatomy, Rostock University Medical Center, D-18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Rolfs","sequence":"additional","affiliation":[{"name":"Centogene AG, Rostock, Am Strande 7, 18055 Rostock, Germany"},{"name":"University of Rostock, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7631-9080","authenticated-orcid":false,"given":"Veronica","family":"Antipova","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, D-18057 Rostock, Germany"},{"name":"Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Macroscopic and Clinical Anatomy, Medical University of Graz, A-8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wree","sequence":"additional","affiliation":[{"name":"Centre of Transdisciplinary Neuroscience Rostock, D-18147 Rostock, Germany"},{"name":"Institute of Anatomy, Rostock University Medical Center, D-18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2147","DOI":"10.1038\/cddis.2016.16","article-title":"Necroptosis in niemann\u2013pick disease, type C1: A potential therapeutic target","volume":"7","author":"Cougnoux","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1194\/jlr.P000331","article-title":"The national niemann-pick type c1 disease database: Correlation of lipid profi les, mutations, and biochemical phenotypes","volume":"51","author":"Garver","year":"2010","journal-title":"J. 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