Genetic-based, differential susceptibility to paraquat neurotoxicity in mice

Lina Yin, Lu Lu, Kavita Prasad, Eric K. Richfield, Erica L. Unger, Jialin Xu, Byron Jones

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Paraquat (PQ) is an herbicide used extensively in agriculture. This agent is also suspected to be a risk factor for Parkinson's disease (PD) by harming nigro-striatal dopamine neurons. There is likely, genetic-based, individual variability in susceptibility to PQ neurotoxicity related PD. In this study, we measured the delivery of PQ to the brain after three weekly injections of PQ at 5mgkg-1, PQ-related neural toxicity after three weekly injections of PQ at 1mgkg-1or 5mgkg-1, PQ-related iron accumulation and PQ-related gene expression in midbrain of DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains after a single injection of PQ at 15mgkg-1 and 10mgkg-1, respectively. Results showed that compared to controls, PQ-treated B6 mice lost greater numbers of dopaminergic neurons in the substantia nigra pars compacta than D2 mice; however, distribution of PQ to the midbrain was equal between the strains. PQ also significantly increased iron concentration in the midbrain of B6 but not D2 mice. Microarray analysis of the ventral midbrain showed greater PQ-induced changes in gene expression in B6 compared to D2 mice. This is the first study to report genetically-based differences in susceptibility to PQ neurotoxicity and to understanding individual differences in vulnerability to PQ neurotoxicity and its relation to PD in humans.

Original languageEnglish (US)
Pages (from-to)415-421
Number of pages7
JournalNeurotoxicology and Teratology
Volume33
Issue number3
DOIs
StatePublished - May 1 2011

Fingerprint

Paraquat
Mesencephalon
Inbred DBA Mouse
Parkinson Disease
Dopaminergic Neurons
Gene expression
Injections
Neurons
Iron
Gene Expression
Corpus Striatum
Inbred Strains Mice
Herbicides
Microarray Analysis
Microarrays
Agriculture
Individuality

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Genetic-based, differential susceptibility to paraquat neurotoxicity in mice. / Yin, Lina; Lu, Lu; Prasad, Kavita; Richfield, Eric K.; Unger, Erica L.; Xu, Jialin; Jones, Byron.

In: Neurotoxicology and Teratology, Vol. 33, No. 3, 01.05.2011, p. 415-421.

Research output: Contribution to journalArticle

Yin, Lina ; Lu, Lu ; Prasad, Kavita ; Richfield, Eric K. ; Unger, Erica L. ; Xu, Jialin ; Jones, Byron. / Genetic-based, differential susceptibility to paraquat neurotoxicity in mice. In: Neurotoxicology and Teratology. 2011 ; Vol. 33, No. 3. pp. 415-421.
@article{f921de712aa94221b0ca1b19d80fc3a1,
title = "Genetic-based, differential susceptibility to paraquat neurotoxicity in mice",
abstract = "Paraquat (PQ) is an herbicide used extensively in agriculture. This agent is also suspected to be a risk factor for Parkinson's disease (PD) by harming nigro-striatal dopamine neurons. There is likely, genetic-based, individual variability in susceptibility to PQ neurotoxicity related PD. In this study, we measured the delivery of PQ to the brain after three weekly injections of PQ at 5mgkg-1, PQ-related neural toxicity after three weekly injections of PQ at 1mgkg-1or 5mgkg-1, PQ-related iron accumulation and PQ-related gene expression in midbrain of DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains after a single injection of PQ at 15mgkg-1 and 10mgkg-1, respectively. Results showed that compared to controls, PQ-treated B6 mice lost greater numbers of dopaminergic neurons in the substantia nigra pars compacta than D2 mice; however, distribution of PQ to the midbrain was equal between the strains. PQ also significantly increased iron concentration in the midbrain of B6 but not D2 mice. Microarray analysis of the ventral midbrain showed greater PQ-induced changes in gene expression in B6 compared to D2 mice. This is the first study to report genetically-based differences in susceptibility to PQ neurotoxicity and to understanding individual differences in vulnerability to PQ neurotoxicity and its relation to PD in humans.",
author = "Lina Yin and Lu Lu and Kavita Prasad and Richfield, {Eric K.} and Unger, {Erica L.} and Jialin Xu and Byron Jones",
year = "2011",
month = "5",
day = "1",
doi = "10.1016/j.ntt.2011.02.012",
language = "English (US)",
volume = "33",
pages = "415--421",
journal = "Neurotoxicology and Teratology",
issn = "0892-0362",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Genetic-based, differential susceptibility to paraquat neurotoxicity in mice

AU - Yin, Lina

AU - Lu, Lu

AU - Prasad, Kavita

AU - Richfield, Eric K.

AU - Unger, Erica L.

AU - Xu, Jialin

AU - Jones, Byron

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Paraquat (PQ) is an herbicide used extensively in agriculture. This agent is also suspected to be a risk factor for Parkinson's disease (PD) by harming nigro-striatal dopamine neurons. There is likely, genetic-based, individual variability in susceptibility to PQ neurotoxicity related PD. In this study, we measured the delivery of PQ to the brain after three weekly injections of PQ at 5mgkg-1, PQ-related neural toxicity after three weekly injections of PQ at 1mgkg-1or 5mgkg-1, PQ-related iron accumulation and PQ-related gene expression in midbrain of DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains after a single injection of PQ at 15mgkg-1 and 10mgkg-1, respectively. Results showed that compared to controls, PQ-treated B6 mice lost greater numbers of dopaminergic neurons in the substantia nigra pars compacta than D2 mice; however, distribution of PQ to the midbrain was equal between the strains. PQ also significantly increased iron concentration in the midbrain of B6 but not D2 mice. Microarray analysis of the ventral midbrain showed greater PQ-induced changes in gene expression in B6 compared to D2 mice. This is the first study to report genetically-based differences in susceptibility to PQ neurotoxicity and to understanding individual differences in vulnerability to PQ neurotoxicity and its relation to PD in humans.

AB - Paraquat (PQ) is an herbicide used extensively in agriculture. This agent is also suspected to be a risk factor for Parkinson's disease (PD) by harming nigro-striatal dopamine neurons. There is likely, genetic-based, individual variability in susceptibility to PQ neurotoxicity related PD. In this study, we measured the delivery of PQ to the brain after three weekly injections of PQ at 5mgkg-1, PQ-related neural toxicity after three weekly injections of PQ at 1mgkg-1or 5mgkg-1, PQ-related iron accumulation and PQ-related gene expression in midbrain of DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains after a single injection of PQ at 15mgkg-1 and 10mgkg-1, respectively. Results showed that compared to controls, PQ-treated B6 mice lost greater numbers of dopaminergic neurons in the substantia nigra pars compacta than D2 mice; however, distribution of PQ to the midbrain was equal between the strains. PQ also significantly increased iron concentration in the midbrain of B6 but not D2 mice. Microarray analysis of the ventral midbrain showed greater PQ-induced changes in gene expression in B6 compared to D2 mice. This is the first study to report genetically-based differences in susceptibility to PQ neurotoxicity and to understanding individual differences in vulnerability to PQ neurotoxicity and its relation to PD in humans.

UR - http://www.scopus.com/inward/record.url?scp=79957811989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957811989&partnerID=8YFLogxK

U2 - 10.1016/j.ntt.2011.02.012

DO - 10.1016/j.ntt.2011.02.012

M3 - Article

VL - 33

SP - 415

EP - 421

JO - Neurotoxicology and Teratology

JF - Neurotoxicology and Teratology

SN - 0892-0362

IS - 3

ER -