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Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

Skene, Debra, Middleton, Benita, Fraser, CK, Pennings, JLA, Kuchel, TR, Rudiger, SR, Bawden, CS and Morton, AJ (2017) Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers Scientific Reports, 7, 43030.

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Abstract

The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients.

Item Type: Article
Subjects : Biosciences and Medicine
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Skene, DebraD.Skene@surrey.ac.ukUNSPECIFIED
Middleton, BenitaB.Middleton@surrey.ac.ukUNSPECIFIED
Fraser, CKUNSPECIFIEDUNSPECIFIED
Pennings, JLAUNSPECIFIEDUNSPECIFIED
Kuchel, TRUNSPECIFIEDUNSPECIFIED
Rudiger, SRUNSPECIFIEDUNSPECIFIED
Bawden, CSUNSPECIFIEDUNSPECIFIED
Morton, AJUNSPECIFIEDUNSPECIFIED
Date : 22 February 2017
Identification Number : 10.1038/srep43030
Copyright Disclaimer : © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Depositing User : Symplectic Elements
Date Deposited : 23 Feb 2017 10:58
Last Modified : 06 Jul 2017 08:53
URI: http://epubs.surrey.ac.uk/id/eprint/813622

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