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Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease

Huntington’s disease (HD) is a progressive, neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. To investigate the metabolic alterations that occur in HD, here we examined plasma and whole‐brain metabolomic profiles of the R6/2 mouse model of HD. Plasma and brain m...

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Autores principales: Hashimoto, Masayo, Watanabe, Kenichi, Miyoshi, Kan, Koyanagi, Yukako, Tadano, Jun, Miyawaki, Izuru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487039/
https://www.ncbi.nlm.nih.gov/pubmed/34469070
http://dx.doi.org/10.1002/2211-5463.13285
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author Hashimoto, Masayo
Watanabe, Kenichi
Miyoshi, Kan
Koyanagi, Yukako
Tadano, Jun
Miyawaki, Izuru
author_facet Hashimoto, Masayo
Watanabe, Kenichi
Miyoshi, Kan
Koyanagi, Yukako
Tadano, Jun
Miyawaki, Izuru
author_sort Hashimoto, Masayo
collection PubMed
description Huntington’s disease (HD) is a progressive, neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. To investigate the metabolic alterations that occur in HD, here we examined plasma and whole‐brain metabolomic profiles of the R6/2 mouse model of HD. Plasma and brain metabolomic analyses were conducted using capillary electrophoresis–mass spectrometry (CE‐MS). In addition, liquid chromatography–mass spectrometry (LC‐MS) was also applied to plasma metabolomic analyses, to cover the broad range of metabolites with various physical and chemical properties. Various metabolic alterations were identified in R6/2 mice. We report for the first time the perturbation of histidine metabolism in the brain of R6/2 mice, which was signaled by decreases in neuroprotective dipeptides and histamine metabolites, indicative of neurodegeneration and an altered histaminergic system. Other differential metabolites were related to arginine metabolism and cysteine and methionine metabolism, suggesting upregulation of the urea cycle, perturbation of energy homeostasis, and an increase in oxidative stress. In addition, remarkable changes in specific lipid classes are indicative of dysregulation of lipid metabolism. These findings provide a deeper insight into the metabolic alterations that occur in HD and provide a foundation for the future development of HD therapeutics.
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spelling pubmed-84870392021-10-07 Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease Hashimoto, Masayo Watanabe, Kenichi Miyoshi, Kan Koyanagi, Yukako Tadano, Jun Miyawaki, Izuru FEBS Open Bio Research Articles Huntington’s disease (HD) is a progressive, neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. To investigate the metabolic alterations that occur in HD, here we examined plasma and whole‐brain metabolomic profiles of the R6/2 mouse model of HD. Plasma and brain metabolomic analyses were conducted using capillary electrophoresis–mass spectrometry (CE‐MS). In addition, liquid chromatography–mass spectrometry (LC‐MS) was also applied to plasma metabolomic analyses, to cover the broad range of metabolites with various physical and chemical properties. Various metabolic alterations were identified in R6/2 mice. We report for the first time the perturbation of histidine metabolism in the brain of R6/2 mice, which was signaled by decreases in neuroprotective dipeptides and histamine metabolites, indicative of neurodegeneration and an altered histaminergic system. Other differential metabolites were related to arginine metabolism and cysteine and methionine metabolism, suggesting upregulation of the urea cycle, perturbation of energy homeostasis, and an increase in oxidative stress. In addition, remarkable changes in specific lipid classes are indicative of dysregulation of lipid metabolism. These findings provide a deeper insight into the metabolic alterations that occur in HD and provide a foundation for the future development of HD therapeutics. John Wiley and Sons Inc. 2021-09-14 /pmc/articles/PMC8487039/ /pubmed/34469070 http://dx.doi.org/10.1002/2211-5463.13285 Text en © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Hashimoto, Masayo
Watanabe, Kenichi
Miyoshi, Kan
Koyanagi, Yukako
Tadano, Jun
Miyawaki, Izuru
Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease
title Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease
title_full Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease
title_fullStr Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease
title_full_unstemmed Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease
title_short Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington’s disease
title_sort multiplatform metabolomic analysis of the r6/2 mouse model of huntington’s disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487039/
https://www.ncbi.nlm.nih.gov/pubmed/34469070
http://dx.doi.org/10.1002/2211-5463.13285
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