Trichloroethylene and Parkinson’s Disease: Risk Assessment

Mei Liu, Eun Joo Shin, Duy Khanh Dang, Chun Hui Jin, Phil Ho Lee, Ji Hoon Jeong, Seok Joo Park, Yong Sun Kim, Bin Xing, Tao Xin, Guoying Bing, Hyoung Chun Kim

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

This study was conducted to investigate the mechanism of action and extent of selective dopaminergic neurodegeneration caused by exposure to trichloroethylene (TCE) leading to the endogenous formation of the neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in rodents. Beginning at 3 months of age, male C57BL/6 mice received oral TCE dissolved in vehicle for 8 months. Dopaminergic neuronal loss was assessed by nigral tyrosine hydroxylase (TH) immunoreactivity. Selective dopaminergic neurodegeneration was determined based on histological analysis of non-dopaminergic neurons in the brain. Behavioral assays were evaluated using open field activity and rotarod tests. Mitochondrial complex I activity, oxidative stress markers, and microglial activation were also examined in the substantia nigra. The level of TaClo was detected using HPLC-electrospray ionization tandem mass spectrometry. Dopaminergic neurotoxicity of TaClo was determined in midbrain organotypic cultures from rat pups. Following 8 months of TCE treatment, there was a progressive and selective loss of 50% of the dopaminergic neurons in mouse substantia nigra (SN) and about 50% loss of dopamine and 72% loss of 3,4-dihydroxyphenylacetic acid in the striatum, respectively. In addition, motor deficits, mitochondrial impairment, oxidative stress, and inflammation were measured. TaClo content was quantified in the brain after TCE treatment. In organotypic cultures, TaClo rather than TCE induced dopaminergic neuronal loss, similar to MPP+. TCE exposure may stimulate the endogenous formation of TaClo, which is responsible for dopaminergic neurodegeneration. However, even prolonged administration of TCE was insufficient for producing a greater than 50% loss of nigral dopamine neurons, indicating that additional co-morbid factors would be needed for mimicking the profound loss of dopamine neurons seen in Parkinson’s disease.

Original languageEnglish
Pages (from-to)6201-6214
Number of pages14
JournalMolecular Neurobiology
Volume55
Issue number7
DOIs
StatePublished - Jul 1 2018

Bibliographical note

Funding Information:
Acknowledgements This study was funded by the following grants: the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (#NRF-2017R1A2B1003346 and #NRF-2016R1A1A1A05005201), Republic of Korea, and the NRF grant funded by the Korea Government (MSIP) (2011-0018355), Republic of Korea.

Publisher Copyright:
© 2017, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

  • 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline
  • Mitochondria
  • Oxidative stress
  • Parkinson’s disease
  • Substantia nigra
  • Trichloroethylene

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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