Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice

Environmental exposure, genetic modification, and aging are considered risky for Parkinson's disease (PD). How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. Paraquat is an herbicide commonly used for weed and grass control. Exposure to paraq...

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Main Authors:	Zhou, Hongxia, Huang, Cao, Tong, Jianbin, Xia, Xu-Gang
Format:	Online
Language:	English
Published:	Ivyspring International Publisher 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204408/

id	pubmed-3204408
recordtype	oai_dc
spelling	pubmed-32044082011-10-31 Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice Zhou, Hongxia Huang, Cao Tong, Jianbin Xia, Xu-Gang Research Paper Environmental exposure, genetic modification, and aging are considered risky for Parkinson's disease (PD). How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. Paraquat is an herbicide commonly used for weed and grass control. Exposure to paraquat is associated with the increased incidence of PD. In contrast to familial PD, most sporadic PD cases do not have genetic mutation, but may suffer from partial dysfunction of neuron-protective genes as aging. Using conditional transgenic RNAi, we showed that temporal silencing of PINK1 expression in adult mice increased striatal dopamine, the phenotype that could not be induced by constitutive gene silencing. Moreover, early exposure to paraquat sensitized dopaminergic neurons to subsequent silencing of PINK1 gene expression, leading to a significant loss of dopaminergic neurons. Our findings suggest a novel pathogenesis of PD: exposure to environmental toxicants early in the life reduces the threshold of developing PD and partial dysfunction of neuron-protective genes later in the life initiates a process of progressive neurodegeneration to cross the reduced threshold of disease onset. Ivyspring International Publisher 2011-10-26 /pmc/articles/PMC3204408/ /pubmed/22043175 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhou, Hongxia Huang, Cao Tong, Jianbin Xia, Xu-Gang
spellingShingle	Zhou, Hongxia Huang, Cao Tong, Jianbin Xia, Xu-Gang Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice
author_facet	Zhou, Hongxia Huang, Cao Tong, Jianbin Xia, Xu-Gang
author_sort	Zhou, Hongxia
title	Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice
title_short	Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice
title_full	Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice
title_fullStr	Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice
title_full_unstemmed	Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice
title_sort	early exposure to paraquat sensitizes dopaminergic neurons to subsequent silencing of pink1 gene expression in mice
description	Environmental exposure, genetic modification, and aging are considered risky for Parkinson's disease (PD). How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. Paraquat is an herbicide commonly used for weed and grass control. Exposure to paraquat is associated with the increased incidence of PD. In contrast to familial PD, most sporadic PD cases do not have genetic mutation, but may suffer from partial dysfunction of neuron-protective genes as aging. Using conditional transgenic RNAi, we showed that temporal silencing of PINK1 expression in adult mice increased striatal dopamine, the phenotype that could not be induced by constitutive gene silencing. Moreover, early exposure to paraquat sensitized dopaminergic neurons to subsequent silencing of PINK1 gene expression, leading to a significant loss of dopaminergic neurons. Our findings suggest a novel pathogenesis of PD: exposure to environmental toxicants early in the life reduces the threshold of developing PD and partial dysfunction of neuron-protective genes later in the life initiates a process of progressive neurodegeneration to cross the reduced threshold of disease onset.
publisher	Ivyspring International Publisher
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204408/
_version_	1611484481332445184

Early Exposure to Paraquat Sensitizes Dopaminergic Neurons to Subsequent Silencing of PINK1 Gene Expression in Mice

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