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Trichloroethylene and Parkinson’s Disease: Risk Assessment

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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.

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Abbreviations

PD:

Parkinson’s disease

TCE:

Trichloroethylene

TaClo:

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

TH:

Tyrosine hydroxylase

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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.

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Author notes

  1. Mei Liu and Eun-Joo Shin contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA

    Mei Liu, Bin Xing & Guoying Bing

  2. Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea

    Eun-Joo Shin, Duy-Khanh Dang, Seok-Joo Park & Hyoung-Chun Kim

  3. Department of Geriatrics, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, 214151, China

    Chun-Hui Jin

  4. National Creative Research Initiative Center for Catalytic Organic Reactions, Department of Chemistry, Kangwon National University, Chunchon, 24341, Republic of Korea

    Phil Ho Lee

  5. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 06974, Republic of Korea

    Ji Hoon Jeong

  6. Ilsong Institute of Life Science, Hallym University, Anyang, 14066, Republic of Korea

    Seok-Joo Park & Yong-Sun Kim

  7. Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, People’s Republic of China

    Tao Xin

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Correspondence to Guoying Bing or Hyoung-Chun Kim.

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Liu, M., Shin, EJ., Dang, DK. et al. Trichloroethylene and Parkinson’s Disease: Risk Assessment. Mol Neurobiol 55, 6201–6214 (2018). https://doi.org/10.1007/s12035-017-0830-x

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