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Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study

Cerebral palsy (CP) is one of the most common causes of motor disability in childhood, with complex and heterogeneous etiopathophysiology and clinical presentation. Understanding the metabolic processes associated with the disease may aid in the discovery of preventive measures and therapy. Tissue s...

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Autores principales: Alpay Savasan, Zeynep, Yilmaz, Ali, Ugur, Zafer, Aydas, Buket, Bahado-Singh, Ray O., Graham, Stewart F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409919/
https://www.ncbi.nlm.nih.gov/pubmed/30717353
http://dx.doi.org/10.3390/metabo9020027
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author Alpay Savasan, Zeynep
Yilmaz, Ali
Ugur, Zafer
Aydas, Buket
Bahado-Singh, Ray O.
Graham, Stewart F.
author_facet Alpay Savasan, Zeynep
Yilmaz, Ali
Ugur, Zafer
Aydas, Buket
Bahado-Singh, Ray O.
Graham, Stewart F.
author_sort Alpay Savasan, Zeynep
collection PubMed
description Cerebral palsy (CP) is one of the most common causes of motor disability in childhood, with complex and heterogeneous etiopathophysiology and clinical presentation. Understanding the metabolic processes associated with the disease may aid in the discovery of preventive measures and therapy. Tissue samples (caudate nucleus) were obtained from post-mortem CP cases (n = 9) and age- and gender-matched control subjects (n = 11). We employed a targeted metabolomics approach using both (1)H NMR and direct injection liquid chromatography-tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 55 metabolites using (1)H NMR and 186 using DI/LC-MS/MS. Among the 222 detected metabolites, 27 showed significant concentration changes between CP cases and controls. Glycerophospholipids and urea were the most commonly selected metabolites used to develop predictive models capable of discriminating between CP and controls. Metabolomics enrichment analysis identified folate, propanoate, and androgen/estrogen metabolism as the top three significantly perturbed pathways. We report for the first time the metabolomic profiling of post-mortem brain tissue from patients who died from cerebral palsy. These findings could help to further investigate the complex etiopathophysiology of CP while identifying predictive, central biomarkers of CP.
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spelling pubmed-64099192019-03-22 Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study Alpay Savasan, Zeynep Yilmaz, Ali Ugur, Zafer Aydas, Buket Bahado-Singh, Ray O. Graham, Stewart F. Metabolites Article Cerebral palsy (CP) is one of the most common causes of motor disability in childhood, with complex and heterogeneous etiopathophysiology and clinical presentation. Understanding the metabolic processes associated with the disease may aid in the discovery of preventive measures and therapy. Tissue samples (caudate nucleus) were obtained from post-mortem CP cases (n = 9) and age- and gender-matched control subjects (n = 11). We employed a targeted metabolomics approach using both (1)H NMR and direct injection liquid chromatography-tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 55 metabolites using (1)H NMR and 186 using DI/LC-MS/MS. Among the 222 detected metabolites, 27 showed significant concentration changes between CP cases and controls. Glycerophospholipids and urea were the most commonly selected metabolites used to develop predictive models capable of discriminating between CP and controls. Metabolomics enrichment analysis identified folate, propanoate, and androgen/estrogen metabolism as the top three significantly perturbed pathways. We report for the first time the metabolomic profiling of post-mortem brain tissue from patients who died from cerebral palsy. These findings could help to further investigate the complex etiopathophysiology of CP while identifying predictive, central biomarkers of CP. MDPI 2019-02-02 /pmc/articles/PMC6409919/ /pubmed/30717353 http://dx.doi.org/10.3390/metabo9020027 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alpay Savasan, Zeynep
Yilmaz, Ali
Ugur, Zafer
Aydas, Buket
Bahado-Singh, Ray O.
Graham, Stewart F.
Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study
title Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study
title_full Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study
title_fullStr Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study
title_full_unstemmed Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study
title_short Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study
title_sort metabolomic profiling of cerebral palsy brain tissue reveals novel central biomarkers and biochemical pathways associated with the disease: a pilot study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409919/
https://www.ncbi.nlm.nih.gov/pubmed/30717353
http://dx.doi.org/10.3390/metabo9020027
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