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Epigenetic analysis in a murine genetic model of Gulf War illness

Of the nearly 1 million military personnel who participated in the 1990–1991 Gulf War, between 25% and 35% became ill with what now is referred to as Gulf War Illness (GWI) by the Department of Defense. Symptoms varied from gastrointestinal distress to lethargy, memory loss, inability to concentrate...

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Autores principales: Mozhui, Khyobeni, O’Callaghan, James P., Ashbrook, David G., Prins, Pjotr, Zhao, Wenyuan, Lu, Lu, Jones, Byron C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300436/
https://www.ncbi.nlm.nih.gov/pubmed/37389175
http://dx.doi.org/10.3389/ftox.2023.1162749
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author Mozhui, Khyobeni
O’Callaghan, James P.
Ashbrook, David G.
Prins, Pjotr
Zhao, Wenyuan
Lu, Lu
Jones, Byron C.
author_facet Mozhui, Khyobeni
O’Callaghan, James P.
Ashbrook, David G.
Prins, Pjotr
Zhao, Wenyuan
Lu, Lu
Jones, Byron C.
author_sort Mozhui, Khyobeni
collection PubMed
description Of the nearly 1 million military personnel who participated in the 1990–1991 Gulf War, between 25% and 35% became ill with what now is referred to as Gulf War Illness (GWI) by the Department of Defense. Symptoms varied from gastrointestinal distress to lethargy, memory loss, inability to concentrate, depression, respiratory, and reproductive problems. The symptoms have persisted for 30 years in those afflicted but the basis of the illness remains largely unknown. Nerve agents and other chemical exposures in the war zone have been implicated but the long-term effects of these acute exposures have left few if any identifiable signatures. The major aim of this study is to elucidate the possible genomic basis for the persistence of symptoms, especially of the neurological and behavioral effects. To address this, we performed a whole genome epigenetic analysis of the proposed cause of GWI, viz., exposure to organophosphate neurotoxicants combined with high circulating glucocorticoids in two inbred mouse strains, C57BL/6J and DBA/2J. The animals received corticosterone in their drinking water for 7 days followed by injection of diisopropylfluorophosphate, a nerve agent surrogate. Six weeks after DFP injection, the animals were euthanized and medial prefrontal cortex harvested for genome-wide DNA methylation analysis using high-throughput sequencing. We observed 67 differentially methylated genes, notably among them, Ttll7, Akr1c14, Slc44a4, and Rusc2, all related to different symptoms of GWI. Our results support proof of principle of genetic differences in the chronic effects of GWI-related exposures and may reveal why the disease has persisted in many of the now aging Gulf War veterans.
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spelling pubmed-103004362023-06-29 Epigenetic analysis in a murine genetic model of Gulf War illness Mozhui, Khyobeni O’Callaghan, James P. Ashbrook, David G. Prins, Pjotr Zhao, Wenyuan Lu, Lu Jones, Byron C. Front Toxicol Toxicology Of the nearly 1 million military personnel who participated in the 1990–1991 Gulf War, between 25% and 35% became ill with what now is referred to as Gulf War Illness (GWI) by the Department of Defense. Symptoms varied from gastrointestinal distress to lethargy, memory loss, inability to concentrate, depression, respiratory, and reproductive problems. The symptoms have persisted for 30 years in those afflicted but the basis of the illness remains largely unknown. Nerve agents and other chemical exposures in the war zone have been implicated but the long-term effects of these acute exposures have left few if any identifiable signatures. The major aim of this study is to elucidate the possible genomic basis for the persistence of symptoms, especially of the neurological and behavioral effects. To address this, we performed a whole genome epigenetic analysis of the proposed cause of GWI, viz., exposure to organophosphate neurotoxicants combined with high circulating glucocorticoids in two inbred mouse strains, C57BL/6J and DBA/2J. The animals received corticosterone in their drinking water for 7 days followed by injection of diisopropylfluorophosphate, a nerve agent surrogate. Six weeks after DFP injection, the animals were euthanized and medial prefrontal cortex harvested for genome-wide DNA methylation analysis using high-throughput sequencing. We observed 67 differentially methylated genes, notably among them, Ttll7, Akr1c14, Slc44a4, and Rusc2, all related to different symptoms of GWI. Our results support proof of principle of genetic differences in the chronic effects of GWI-related exposures and may reveal why the disease has persisted in many of the now aging Gulf War veterans. Frontiers Media S.A. 2023-06-14 /pmc/articles/PMC10300436/ /pubmed/37389175 http://dx.doi.org/10.3389/ftox.2023.1162749 Text en Copyright © 2023 Mozhui, O’Callaghan, Ashbrook, Prins, Zhao, Lu and Jones. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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 Toxicology
Mozhui, Khyobeni
O’Callaghan, James P.
Ashbrook, David G.
Prins, Pjotr
Zhao, Wenyuan
Lu, Lu
Jones, Byron C.
Epigenetic analysis in a murine genetic model of Gulf War illness
title Epigenetic analysis in a murine genetic model of Gulf War illness
title_full Epigenetic analysis in a murine genetic model of Gulf War illness
title_fullStr Epigenetic analysis in a murine genetic model of Gulf War illness
title_full_unstemmed Epigenetic analysis in a murine genetic model of Gulf War illness
title_short Epigenetic analysis in a murine genetic model of Gulf War illness
title_sort epigenetic analysis in a murine genetic model of gulf war illness
topic Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300436/
https://www.ncbi.nlm.nih.gov/pubmed/37389175
http://dx.doi.org/10.3389/ftox.2023.1162749
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