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Mol Neurobiol. 2018 Jul;55(7):6201-6214. doi: 10.1007/s12035-017-0830-x. Epub 2017 Dec 22.

Trichloroethylene and Parkinson's Disease: Risk Assessment.

Author information

1
Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA.
2
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea.
3
Department of Geriatrics, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, 214151, China.
4
National Creative Research Initiative Center for Catalytic Organic Reactions, Department of Chemistry, Kangwon National University, Chunchon, 24341, Republic of Korea.
5
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 06974, Republic of Korea.
6
Ilsong Institute of Life Science, Hallym University, Anyang, 14066, Republic of Korea.
7
Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, People's Republic of China.
8
Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA. gbing@uky.edu.
9
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea. kimhc@kangwon.ac.kr.

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:

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

PMID:
29270919
DOI:
10.1007/s12035-017-0830-x

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