Gender-Specific Effects of Two Treatment Strategies in a Mouse Model of Niemann-Pick Disease Type C1
Open Access
- 3 March 2021
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (5), 2539
- https://doi.org/10.3390/ijms22052539
Abstract
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-β-cyclodextrin (HPßCD) 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 HPßCD alone on body and brain weight and the behavior of NPC1−/− mice in a larger cohort, with special reference to gender differences. A total of 117 NPC1−/− and 123 NPC1+/+ mice underwent either COMBI, MIGLU only, HPßCD only, or vehicle treatment (Sham), or received no treatment at all (None). In male and female NPC1−/− 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−/− mice benefited from COMBI treatment, whereas female mice benefited from COMBI, MIGLU, and HPßCD treatment. As seen in the open field test, the reduced locomotor activity of male and female NPC1−/− mice was not significantly ameliorated in either treatment group. Our results suggest that in NPC1−/− 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−/− mice was almost completely reduced only in the female groups.Funding Information
- Centre of Transdisciplinary Neuroscience Rostock (Support)
This publication has 158 references indexed in Scilit:
- Niemann-Pick disease type C clinical database: cognitive and coordination deficits are early disease indicatorsOrphanet Journal of Rare Diseases, 2013
- Disease and patient characteristics in NP-C patients: findings from an international disease registryOrphanet Journal of Rare Diseases, 2013
- Niemann-Pick Disease Type C: Implications for Sedation and Anesthesia for Diagnostic ProceduresJournal of Child Neurology, 2012
- Dysphagia as a risk factor for mortality in Niemann-Pick disease type C: systematic literature review and evidence from studies with miglustatOrphanet Journal of Rare Diseases, 2012
- Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1−/− miceMolecular Genetics and Metabolism, 2011
- Niemann-Pick disease type COrphanet Journal of Rare Diseases, 2010
- Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acidJournal of Lipid Research, 2010
- The National Niemann-Pick Type C1 Disease Database: correlation of lipid profiles, mutations, and biochemical phenotypesJournal of Lipid Research, 2010
- Amelioration of enteric neuropathology in a mouse model of Niemann-Pick C by Npc1 expression in enteric gliaJournal of Neuroscience Research, 2009
- Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1 −/− mouseProceedings of the National Academy of Sciences of the United States of America, 2009