Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.

Parkinson's disease (PD) is a multifactorial disease known to result from a variety of factors. Although age is the principal risk factor, other etiological mechanisms have been identified, including gene mutations and exposure to toxins. Deregulation of energy metabolism, mostly through the lo...

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Autores principales:	Pierre O Poliquin, Jingkui Chen, Mathieu Cloutier, Louis-Éric Trudeau, Mario Jolicoeur
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9835fb7fa69548c4a94c0c2add482d44
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spelling	oai:doaj.org-article:9835fb7fa69548c4a94c0c2add482d442021-11-18T09:03:21ZMetabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.1932-620310.1371/journal.pone.0069146https://doaj.org/article/9835fb7fa69548c4a94c0c2add482d442013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935941/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Parkinson's disease (PD) is a multifactorial disease known to result from a variety of factors. Although age is the principal risk factor, other etiological mechanisms have been identified, including gene mutations and exposure to toxins. Deregulation of energy metabolism, mostly through the loss of complex I efficiency, is involved in disease progression in both the genetic and sporadic forms of the disease. In this study, we investigated energy deregulation in the cerebral tissue of animal models (genetic and toxin induced) of PD using an approach that combines metabolomics and mathematical modelling. In a first step, quantitative measurements of energy-related metabolites in mouse brain slices revealed most affected pathways. A genetic model of PD, the Park2 knockout, was compared to the effect of CCCP, a mitochondrial uncoupler [corrected]. Model simulated and experimental results revealed a significant and sustained decrease in ATP after CCCP exposure, but not in the genetic mice model. In support to data analysis, a mathematical model of the relevant metabolic pathways was developed and calibrated onto experimental data. In this work, we show that a short-term stress response in nucleotide scavenging is most probably induced by the toxin exposure. In turn, the robustness of energy-related pathways in the model explains how genetic perturbations, at least in young animals, are not sufficient to induce significant changes at the metabolite level.Pierre O PoliquinJingkui ChenMathieu CloutierLouis-Éric TrudeauMario JolicoeurPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69146 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pierre O Poliquin Jingkui Chen Mathieu Cloutier Louis-Éric Trudeau Mario Jolicoeur Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.
description	Parkinson's disease (PD) is a multifactorial disease known to result from a variety of factors. Although age is the principal risk factor, other etiological mechanisms have been identified, including gene mutations and exposure to toxins. Deregulation of energy metabolism, mostly through the loss of complex I efficiency, is involved in disease progression in both the genetic and sporadic forms of the disease. In this study, we investigated energy deregulation in the cerebral tissue of animal models (genetic and toxin induced) of PD using an approach that combines metabolomics and mathematical modelling. In a first step, quantitative measurements of energy-related metabolites in mouse brain slices revealed most affected pathways. A genetic model of PD, the Park2 knockout, was compared to the effect of CCCP, a mitochondrial uncoupler [corrected]. Model simulated and experimental results revealed a significant and sustained decrease in ATP after CCCP exposure, but not in the genetic mice model. In support to data analysis, a mathematical model of the relevant metabolic pathways was developed and calibrated onto experimental data. In this work, we show that a short-term stress response in nucleotide scavenging is most probably induced by the toxin exposure. In turn, the robustness of energy-related pathways in the model explains how genetic perturbations, at least in young animals, are not sufficient to induce significant changes at the metabolite level.
format	article
author	Pierre O Poliquin Jingkui Chen Mathieu Cloutier Louis-Éric Trudeau Mario Jolicoeur
author_facet	Pierre O Poliquin Jingkui Chen Mathieu Cloutier Louis-Éric Trudeau Mario Jolicoeur
author_sort	Pierre O Poliquin
title	Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.
title_short	Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.
title_full	Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.
title_fullStr	Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.
title_full_unstemmed	Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.
title_sort	metabolomics and in-silico analysis reveal critical energy deregulations in animal models of parkinson's disease.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9835fb7fa69548c4a94c0c2add482d44
work_keys_str_mv	AT pierreopoliquin metabolomicsandinsilicoanalysisrevealcriticalenergyderegulationsinanimalmodelsofparkinsonsdisease AT jingkuichen metabolomicsandinsilicoanalysisrevealcriticalenergyderegulationsinanimalmodelsofparkinsonsdisease AT mathieucloutier metabolomicsandinsilicoanalysisrevealcriticalenergyderegulationsinanimalmodelsofparkinsonsdisease AT louiserictrudeau metabolomicsandinsilicoanalysisrevealcriticalenergyderegulationsinanimalmodelsofparkinsonsdisease AT mariojolicoeur metabolomicsandinsilicoanalysisrevealcriticalenergyderegulationsinanimalmodelsofparkinsonsdisease
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Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.

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