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Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring

Early-life exposure (from postnatal day 6 to postnatal day 21) to permethrin has been associated with long-term development of dopaminergic neurodegeneration in rats. Here, we first investigated if the dopamine decrease observed following early postnatal exposure to permethrin, an oxidative stressor...

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Autores principales: Bordoni, Laura, Nasuti, Cinzia, Di Stefano, Antonio, Marinelli, Lisa, Gabbianelli, Rosita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399534/
https://www.ncbi.nlm.nih.gov/pubmed/30915194
http://dx.doi.org/10.1155/2019/1472623
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author Bordoni, Laura
Nasuti, Cinzia
Di Stefano, Antonio
Marinelli, Lisa
Gabbianelli, Rosita
author_facet Bordoni, Laura
Nasuti, Cinzia
Di Stefano, Antonio
Marinelli, Lisa
Gabbianelli, Rosita
author_sort Bordoni, Laura
collection PubMed
description Early-life exposure (from postnatal day 6 to postnatal day 21) to permethrin has been associated with long-term development of dopaminergic neurodegeneration in rats. Here, we first investigated if the dopamine decrease observed following early postnatal exposure to permethrin, an oxidative stressor, can impair the dopamine level in the brain of their untreated offspring. Secondly, we evaluated whether this adverse event affects the epigenome of both directly exposed rats (F0) and their untreated offspring (F1). The results show that early-life exposure to the stressor is associated with changes in global DNA methylation and hydroxymethylation in adult age. Furthermore, parental exposure leads to a significant reduction in dopamine level in the offspring (F1) born from parents or just mothers early-life treated (72.72% and 47.35%, respectively). About 2/3 of pups from exposed mothers showed a significant reduction in dopamine level compared to controls. Global DNA methylation and hydroxymethylation impairment was associated with the F1 pups that showed reduced dopamine. This study provides pivotal evidences on intergenerational effects of postnatal exposure to permethrin emphasizing that this xenobiotic can influence the epigenetic memory of early-life parental perturbations disturbing offspring health.
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spelling pubmed-63995342019-03-26 Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring Bordoni, Laura Nasuti, Cinzia Di Stefano, Antonio Marinelli, Lisa Gabbianelli, Rosita Oxid Med Cell Longev Research Article Early-life exposure (from postnatal day 6 to postnatal day 21) to permethrin has been associated with long-term development of dopaminergic neurodegeneration in rats. Here, we first investigated if the dopamine decrease observed following early postnatal exposure to permethrin, an oxidative stressor, can impair the dopamine level in the brain of their untreated offspring. Secondly, we evaluated whether this adverse event affects the epigenome of both directly exposed rats (F0) and their untreated offspring (F1). The results show that early-life exposure to the stressor is associated with changes in global DNA methylation and hydroxymethylation in adult age. Furthermore, parental exposure leads to a significant reduction in dopamine level in the offspring (F1) born from parents or just mothers early-life treated (72.72% and 47.35%, respectively). About 2/3 of pups from exposed mothers showed a significant reduction in dopamine level compared to controls. Global DNA methylation and hydroxymethylation impairment was associated with the F1 pups that showed reduced dopamine. This study provides pivotal evidences on intergenerational effects of postnatal exposure to permethrin emphasizing that this xenobiotic can influence the epigenetic memory of early-life parental perturbations disturbing offspring health. Hindawi 2019-02-19 /pmc/articles/PMC6399534/ /pubmed/30915194 http://dx.doi.org/10.1155/2019/1472623 Text en Copyright © 2019 Laura Bordoni et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bordoni, Laura
Nasuti, Cinzia
Di Stefano, Antonio
Marinelli, Lisa
Gabbianelli, Rosita
Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring
title Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring
title_full Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring
title_fullStr Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring
title_full_unstemmed Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring
title_short Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring
title_sort epigenetic memory of early-life parental perturbation: dopamine decrease and dna methylation changes in offspring
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399534/
https://www.ncbi.nlm.nih.gov/pubmed/30915194
http://dx.doi.org/10.1155/2019/1472623
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