Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Pfalzer, Anna C.a; b; 1 | Wages, Phillip A.d; e; 1 | Porter, Ned A.d; e; f; g | Bowman, Aaron B.a; b; c; g; h; *
Affiliations: [a] Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA | [b] Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA | [c] Vanderbilt Center in Molecular Toxicology, Vanderbilt University Medical Center, Nashville, TN, USA | [d] Department of Chemistry, Vanderbilt University, Nashville, TN, USA | [e] Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, USA | [f] Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA | [g] Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA | [h] School of Health Sciences, Purdue University, West Lafayette, IN, USA
Correspondence: [*] Correspondence to: Aaron B. Bowman, 550 Stadium Mall Drive – HAMP 1173A, West Lafayette, IN 47907-2051, USA. Tel.: +1 765 494 2684; E-mail: bowma117@Purdue.edu.
Note: [1] These authors contributed equally to this work.
Abstract: Background:Cholesterol is necessary for proper neurodevelopment and neuronal health. The brain relies on neural and astrocytic de novo cholesterol synthesis. Huntington’s disease presents with altered levels of cholesterol precursors however it is unknown when the disruption in this molecular pathway occurs and whether Manganese (Mn) may alter these metabolic alterations. Objective:To examine the effect of Mn exposure on cholesterol biosynthesis in pre-manifest and manifest Huntington’s disease mice. Methods:12-week (pre-manifest) male and female and 42-week old (manifest) female YAC128 and littermate control (WT) mice received 3 subcutaneous Mn or vehicle injections. Animals were sacrificed 24 hours after the final injection and striatum, cerebral cortex and cerebellum were collected to measure cholesterol and cholesterol precursors using LC/MS-MS. Results:Striatal desmosterol and cholesterol are increased in pre-manifest HD females compared to age-matched WT female mice. Striatal lanosterol, 8-DHC and desmosterol and cholesterol are reduced in manifest HD females compared to age-and sex-matched WT mice with minimal effects in the cortex and cerebellum. Mn treatment had no effect in the pre-manifest or manifest female brain except reduced lanosterol levels in the cortex of pre-manifest female mice. Neither Mn or HD altered brain cholesterol precursor levels in the pre-manifest HD or WT male mouse. Conclusions:Cholesterol biosynthesis is impaired in early disease stage in female HD mice only and continues throughout disease. These alterations appear largely striatal-specific. Acute systemic exposure to Mn did not significantly alter cholesterol biosynthesis in the striatum at any disease stage.
Keywords: Cholesterol, huntington’s disease, manganese, sterols, striatum
DOI: 10.3233/JHD-180321
Journal: Journal of Huntington's Disease, vol. 8, no. 2, pp. 161-169, 2019
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
sales@iospress.com
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
info@iospress.nl
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office info@iospress.nl
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
china@iospress.cn
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
如果您在出版方面需要帮助或有任何建, 件至: editorial@iospress.nl