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Molecular Neurobiology

, Volume 55, Issue 7, pp 6201–6214 | Cite as

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
Article

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.

Keywords

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

Abbreviations

PD

Parkinson’s disease

TCE

Trichloroethylene

TaClo

1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline

TH

Tyrosine hydroxylase

Notes

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.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interests.

Supplementary material

12035_2017_830_MOESM1_ESM.docx (37 kb)
ESM 1 (DOCX 37 kb).
12035_2017_830_MOESM2_ESM.pdf (3.7 mb)
ESM 2 (PDF 3752 kb).

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Authors and Affiliations

  1. 1.Department of Neuroscience, College of MedicineUniversity of KentuckyLexingtonUSA
  2. 2.Neuropsychopharmacology and Toxicology Program, College of PharmacyKangwon National UniversityChunchonRepublic of Korea
  3. 3.Department of Geriatrics, Wuxi Mental Health CenterNanjing Medical UniversityWuxiChina
  4. 4.National Creative Research Initiative Center for Catalytic Organic Reactions, Department of ChemistryKangwon National UniversityChunchonRepublic of Korea
  5. 5.Department of Pharmacology, College of MedicineChung-Ang UniversitySeoulRepublic of Korea
  6. 6.Ilsong Institute of Life ScienceHallym UniversityAnyangRepublic of Korea
  7. 7.Department of NeurosurgeryProvincial Hospital Affiliated to Shandong UniversityJinanPeople’s Republic of China

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