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

Details

• Personal Author:
  Jones BC ; Lu L ; Mulligan MK ; O'Callaghan JP ; Torres-Rojas C ; Williams RW ; Zhao W ; Zhuang D
• 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. [Description provided by NIOSH]
• Subjects:
  Animals Genetics Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Animal Studies Author Keywords: Tyrosine Hydroxylase BXD Mice Forward Genetic Analysis Neurological Disorders Neurophysiological Effects Neurotoxic Effects Paraquat Paraquat Dichloride Parkinsons Disease Sporadic Parkinson's Disease Stereology

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• ISSN:
  2673-3080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; OSHA Region 4 ; Tennessee ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  3
• NIOSHTIC Number:
  nn:20066159
• Citation:
  Front Toxicol 2021 Nov; 3:722518
• Contact Point Address:
  Byron C. Jones, Department of Genetics, Genomics and Informatics, The University of Tennessee Health Science Center, Memphis, TN, United States
• Email:
  bjone129@uthsc.edu
• CAS Registry Number:
  Methyl viologen (CAS RN 1910-42-5)
• Federal Fiscal Year:
  2022
• Peer Reviewed:
  True
• Source Full Name:
  Frontiers in Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e5767207cc4df9d1d40295baa746ef16eb98fc5b000a1939629407a14b584e83c044ddd7c9fc5ae19c299cb63c7dcded2df0a9770914c9f185a7c532e460e433
• Download URL:
  https://stacks.cdc.gov/view/cdc/212664/cdc_212664_DS1.pdf
• File Type:
  [PDF - 2.12 MB ]