Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease

In Huntington disease (HD), there is increasing evidence for a link between mutant huntingtin expression, mitochondrial dysfunction, energetic deficits and neurodegeneration but the precise nature, causes and order of these events remain to be determined. In this work, our objective was to evaluate...

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Autores principales: Gouarné, Caroline, Tardif, Gwenaëlle, Tracz, Jennifer, Latyszenok, Virginie, Michaud, Magali, Clemens, Laura Emily, Yu-Taeger, Libo, Nguyen, Huu Phuc, Bordet, Thierry, Pruss, Rebecca M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841140/
https://www.ncbi.nlm.nih.gov/pubmed/24303051
http://dx.doi.org/10.1371/journal.pone.0081528
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author Gouarné, Caroline
Tardif, Gwenaëlle
Tracz, Jennifer
Latyszenok, Virginie
Michaud, Magali
Clemens, Laura Emily
Yu-Taeger, Libo
Nguyen, Huu Phuc
Bordet, Thierry
Pruss, Rebecca M.
author_facet Gouarné, Caroline
Tardif, Gwenaëlle
Tracz, Jennifer
Latyszenok, Virginie
Michaud, Magali
Clemens, Laura Emily
Yu-Taeger, Libo
Nguyen, Huu Phuc
Bordet, Thierry
Pruss, Rebecca M.
author_sort Gouarné, Caroline
collection PubMed
description In Huntington disease (HD), there is increasing evidence for a link between mutant huntingtin expression, mitochondrial dysfunction, energetic deficits and neurodegeneration but the precise nature, causes and order of these events remain to be determined. In this work, our objective was to evaluate mitochondrial respiratory function in intact, non-permeabilized, neurons derived from a transgenic rat model for HD compared to their wild type littermates by measuring oxygen consumption rates and extracellular acidification rates. Although HD striatal neurons had similar respiratory capacity as those from their wild-type littermates when they were incubated in rich medium containing a supra-physiological glucose concentration (25 mM), pyruvate and amino acids, respiratory defects emerged when cells were incubated in media containing only a physiological cerebral level of glucose (2.5 mM). According to the concept that glucose is not the sole substrate used by the brain for neuronal energy production, we provide evidence that primary neurons can use lactate as well as pyruvate to fuel the mitochondrial respiratory chain. In contrast to glucose, we found no major deficits in HD striatal neurons’ capacity to use pyruvate as a respiratory substrate compared to wild type littermates. Additionally, we used extracellular acidification rates to confirm a reduction in anaerobic glycolysis in the same cells. Interestingly, the metabolic disturbances observed in striatal neurons were not seen in primary cortical neurons, a brain region affected in later stages of HD. In conclusion, our results argue for a dysfunction in glycolysis, which might precede any defects in the respiratory chain itself, and these are early events in the onset of disease.
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spelling pubmed-38411402013-12-03 Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease Gouarné, Caroline Tardif, Gwenaëlle Tracz, Jennifer Latyszenok, Virginie Michaud, Magali Clemens, Laura Emily Yu-Taeger, Libo Nguyen, Huu Phuc Bordet, Thierry Pruss, Rebecca M. PLoS One Research Article In Huntington disease (HD), there is increasing evidence for a link between mutant huntingtin expression, mitochondrial dysfunction, energetic deficits and neurodegeneration but the precise nature, causes and order of these events remain to be determined. In this work, our objective was to evaluate mitochondrial respiratory function in intact, non-permeabilized, neurons derived from a transgenic rat model for HD compared to their wild type littermates by measuring oxygen consumption rates and extracellular acidification rates. Although HD striatal neurons had similar respiratory capacity as those from their wild-type littermates when they were incubated in rich medium containing a supra-physiological glucose concentration (25 mM), pyruvate and amino acids, respiratory defects emerged when cells were incubated in media containing only a physiological cerebral level of glucose (2.5 mM). According to the concept that glucose is not the sole substrate used by the brain for neuronal energy production, we provide evidence that primary neurons can use lactate as well as pyruvate to fuel the mitochondrial respiratory chain. In contrast to glucose, we found no major deficits in HD striatal neurons’ capacity to use pyruvate as a respiratory substrate compared to wild type littermates. Additionally, we used extracellular acidification rates to confirm a reduction in anaerobic glycolysis in the same cells. Interestingly, the metabolic disturbances observed in striatal neurons were not seen in primary cortical neurons, a brain region affected in later stages of HD. In conclusion, our results argue for a dysfunction in glycolysis, which might precede any defects in the respiratory chain itself, and these are early events in the onset of disease. Public Library of Science 2013-11-26 /pmc/articles/PMC3841140/ /pubmed/24303051 http://dx.doi.org/10.1371/journal.pone.0081528 Text en © 2013 Caroline Gouarné http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gouarné, Caroline
Tardif, Gwenaëlle
Tracz, Jennifer
Latyszenok, Virginie
Michaud, Magali
Clemens, Laura Emily
Yu-Taeger, Libo
Nguyen, Huu Phuc
Bordet, Thierry
Pruss, Rebecca M.
Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease
title Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease
title_full Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease
title_fullStr Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease
title_full_unstemmed Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease
title_short Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease
title_sort early deficits in glycolysis are specific to striatal neurons from a rat model of huntington disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841140/
https://www.ncbi.nlm.nih.gov/pubmed/24303051
http://dx.doi.org/10.1371/journal.pone.0081528
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