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A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions

Nucleic acid protection is a substantial challenge for neurons, which are continuously exposed to oxidative stress in the brain. Neurons require powerful mechanisms to protect DNA and RNA integrity and ensure their functionality and longevity. Beside its well known role in microtubule dynamics, we r...

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Autores principales: Violet, Marie, Delattre, Lucie, Tardivel, Meryem, Sultan, Audrey, Chauderlier, Alban, Caillierez, Raphaelle, Talahari, Smail, Nesslany, Fabrice, Lefebvre, Bruno, Bonnefoy, Eliette, Buée, Luc, Galas, Marie-Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957276/
https://www.ncbi.nlm.nih.gov/pubmed/24672431
http://dx.doi.org/10.3389/fncel.2014.00084
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author Violet, Marie
Delattre, Lucie
Tardivel, Meryem
Sultan, Audrey
Chauderlier, Alban
Caillierez, Raphaelle
Talahari, Smail
Nesslany, Fabrice
Lefebvre, Bruno
Bonnefoy, Eliette
Buée, Luc
Galas, Marie-Christine
author_facet Violet, Marie
Delattre, Lucie
Tardivel, Meryem
Sultan, Audrey
Chauderlier, Alban
Caillierez, Raphaelle
Talahari, Smail
Nesslany, Fabrice
Lefebvre, Bruno
Bonnefoy, Eliette
Buée, Luc
Galas, Marie-Christine
author_sort Violet, Marie
collection PubMed
description Nucleic acid protection is a substantial challenge for neurons, which are continuously exposed to oxidative stress in the brain. Neurons require powerful mechanisms to protect DNA and RNA integrity and ensure their functionality and longevity. Beside its well known role in microtubule dynamics, we recently discovered that Tau is also a key nuclear player in the protection of neuronal genomic DNA integrity under reactive oxygen species (ROS)-inducing heat stress (HS) conditions in primary neuronal cultures. In this report, we analyzed the capacity of Tau to protect neuronal DNA integrity in vivo in adult mice under physiological and HS conditions. We designed an in vivo mouse model of hyperthermia/HS to induce a transient increase in ROS production in the brain. Comet and Terminal deoxyribonucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assays demonstrated that Tau protected genomic DNA in adult cortical and hippocampal neurons in vivo under physiological conditions in wild-type (WT) and Tau-deficient (KO-Tau) mice. HS increased DNA breaks in KO-Tau neurons. Notably, KO-Tau hippocampal neurons in the CA1 subfield restored DNA integrity after HS more weakly than the dentate gyrus (DG) neurons. The formation of phosphorylated histone H2AX foci, a double-strand break marker, was observed in KO-Tau neurons only after HS, indicating that Tau deletion did not trigger similar DNA damage under physiological or HS conditions. Moreover, genomic DNA and cytoplasmic and nuclear RNA integrity were altered under HS in hippocampal neurons exhibiting Tau deficiency, which suggests that Tau also modulates RNA metabolism. Our results suggest that Tau alterations lead to a loss of its nucleic acid safeguarding functions and participate in the accumulation of DNA and RNA oxidative damage observed in the Alzheimer’s disease (AD) brain.
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spelling pubmed-39572762014-03-26 A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions Violet, Marie Delattre, Lucie Tardivel, Meryem Sultan, Audrey Chauderlier, Alban Caillierez, Raphaelle Talahari, Smail Nesslany, Fabrice Lefebvre, Bruno Bonnefoy, Eliette Buée, Luc Galas, Marie-Christine Front Cell Neurosci Neuroscience Nucleic acid protection is a substantial challenge for neurons, which are continuously exposed to oxidative stress in the brain. Neurons require powerful mechanisms to protect DNA and RNA integrity and ensure their functionality and longevity. Beside its well known role in microtubule dynamics, we recently discovered that Tau is also a key nuclear player in the protection of neuronal genomic DNA integrity under reactive oxygen species (ROS)-inducing heat stress (HS) conditions in primary neuronal cultures. In this report, we analyzed the capacity of Tau to protect neuronal DNA integrity in vivo in adult mice under physiological and HS conditions. We designed an in vivo mouse model of hyperthermia/HS to induce a transient increase in ROS production in the brain. Comet and Terminal deoxyribonucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assays demonstrated that Tau protected genomic DNA in adult cortical and hippocampal neurons in vivo under physiological conditions in wild-type (WT) and Tau-deficient (KO-Tau) mice. HS increased DNA breaks in KO-Tau neurons. Notably, KO-Tau hippocampal neurons in the CA1 subfield restored DNA integrity after HS more weakly than the dentate gyrus (DG) neurons. The formation of phosphorylated histone H2AX foci, a double-strand break marker, was observed in KO-Tau neurons only after HS, indicating that Tau deletion did not trigger similar DNA damage under physiological or HS conditions. Moreover, genomic DNA and cytoplasmic and nuclear RNA integrity were altered under HS in hippocampal neurons exhibiting Tau deficiency, which suggests that Tau also modulates RNA metabolism. Our results suggest that Tau alterations lead to a loss of its nucleic acid safeguarding functions and participate in the accumulation of DNA and RNA oxidative damage observed in the Alzheimer’s disease (AD) brain. Frontiers Media S.A. 2014-03-18 /pmc/articles/PMC3957276/ /pubmed/24672431 http://dx.doi.org/10.3389/fncel.2014.00084 Text en Copyright © 2014 Violet, Delattre, Tardivel, Sultan, Chauderlier, Caillierez, Talahari, Nesslany, Lefebvre, Bonnefoy, Buée and Galas. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Violet, Marie
Delattre, Lucie
Tardivel, Meryem
Sultan, Audrey
Chauderlier, Alban
Caillierez, Raphaelle
Talahari, Smail
Nesslany, Fabrice
Lefebvre, Bruno
Bonnefoy, Eliette
Buée, Luc
Galas, Marie-Christine
A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions
title A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions
title_full A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions
title_fullStr A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions
title_full_unstemmed A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions
title_short A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions
title_sort major role for tau in neuronal dna and rna protection in vivo under physiological and hyperthermic conditions
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957276/
https://www.ncbi.nlm.nih.gov/pubmed/24672431
http://dx.doi.org/10.3389/fncel.2014.00084
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