Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice

Paraquat (PQ) is a putative risk factor for the development of sporadic Parkinson’s disease. To model a possible genetic basis for individual differences in susceptibility to exposure to PQ, we recently examined the effects of paraquat on tyrosine hydroxylase (TH)-containing neurons in the substanti...

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Autores principales:	Carolina Torres-Rojas, Wenyuan Zhao, Daming Zhuang, James P. O’Callaghan, Lu Lu, Megan K. Mulligan, Robert W. Williams, Byron C. Jones
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tyrosine hydroxylase sporadic Parkinson’s disease stereology BXD mice forward genetic analysis Toxicology. Poisons RA1190-1270
Acceso en línea:	https://doaj.org/article/6cff8f40b738499d8ee7e55acd2b2020
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spelling	oai:doaj.org-article:6cff8f40b738499d8ee7e55acd2b20202021-11-11T07:58:07ZParaquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice2673-308010.3389/ftox.2021.722518https://doaj.org/article/6cff8f40b738499d8ee7e55acd2b20202021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/ftox.2021.722518/fullhttps://doaj.org/toc/2673-3080Paraquat (PQ) is a putative risk factor for the development of sporadic Parkinson’s disease. To model a possible genetic basis for individual differences in susceptibility to exposure to PQ, we recently examined the effects of paraquat on tyrosine hydroxylase (TH)-containing neurons in the substantia nigra pars compacta (SNc) of six members of the BXD family of mice (n = 2–6 per strain). We injected males with 5 mg/kg paraquat weekly three times. The density of TH+ neurons counted by immunocytochemistry at 200x in eight or more sections through the SNc is reduced in five of the six strains relative to control (N = 4 ± 2 mice per strain). TH+ loss ranged from 0 to 20% with an SEM of 1%. The heritability was estimated using standard ANOVA and jackknife resampling and is 0.37 ± 0.05 in untreated animals and 0.47 ± 0.04 in treated animals. These results demonstrate genetic modulation and GxE variation in susceptibility to PQ exposure and the loss of TH staining in the substantia nigra.Carolina Torres-RojasWenyuan ZhaoDaming ZhuangJames P. O’CallaghanLu LuMegan K. MulliganRobert W. WilliamsByron C. JonesFrontiers Media S.A.articletyrosine hydroxylasesporadic Parkinson’s diseasestereologyBXD miceforward genetic analysisToxicology. PoisonsRA1190-1270ENFrontiers in Toxicology, Vol 3 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tyrosine hydroxylase sporadic Parkinson’s disease stereology BXD mice forward genetic analysis Toxicology. Poisons RA1190-1270
spellingShingle	tyrosine hydroxylase sporadic Parkinson’s disease stereology BXD mice forward genetic analysis Toxicology. Poisons RA1190-1270 Carolina Torres-Rojas Wenyuan Zhao Daming Zhuang James P. O’Callaghan Lu Lu Megan K. Mulligan Robert W. Williams Byron C. Jones Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice
description	Paraquat (PQ) is a putative risk factor for the development of sporadic Parkinson’s disease. To model a possible genetic basis for individual differences in susceptibility to exposure to PQ, we recently examined the effects of paraquat on tyrosine hydroxylase (TH)-containing neurons in the substantia nigra pars compacta (SNc) of six members of the BXD family of mice (n = 2–6 per strain). We injected males with 5 mg/kg paraquat weekly three times. The density of TH+ neurons counted by immunocytochemistry at 200x in eight or more sections through the SNc is reduced in five of the six strains relative to control (N = 4 ± 2 mice per strain). TH+ loss ranged from 0 to 20% with an SEM of 1%. The heritability was estimated using standard ANOVA and jackknife resampling and is 0.37 ± 0.05 in untreated animals and 0.47 ± 0.04 in treated animals. These results demonstrate genetic modulation and GxE variation in susceptibility to PQ exposure and the loss of TH staining in the substantia nigra.
format	article
author	Carolina Torres-Rojas Wenyuan Zhao Daming Zhuang James P. O’Callaghan Lu Lu Megan K. Mulligan Robert W. Williams Byron C. Jones
author_facet	Carolina Torres-Rojas Wenyuan Zhao Daming Zhuang James P. O’Callaghan Lu Lu Megan K. Mulligan Robert W. Williams Byron C. Jones
author_sort	Carolina Torres-Rojas
title	Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice
title_short	Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice
title_full	Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice
title_fullStr	Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice
title_full_unstemmed	Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice
title_sort	paraquat toxicogenetics: strain-related reduction of tyrosine hydroxylase staining in substantia nigra in mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6cff8f40b738499d8ee7e55acd2b2020
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Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice

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