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Trichloroethylene and its metabolite TaClo lead to degeneration of substantia nigra dopaminergic neurones: Effects in wild type and human A30P mutant α-synuclein mice

Lookup NU author(s): Dr Paul Keane, Dr Peter Hanson, Lina Patterson, Professor Peter Blain CBE, Philippa Hepplewhite, Dr Ahmad Khundakar, Dr Sarah Judge, Dr Fiona LeBeau, Dr Christopher Morris

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Parkinson's disease (PD) is characterised pathologically by degeneration of the dopaminergic (DA) neurones of the substantia nigra pars compacta (SNpc) and the presence of α-synuclein containing Lewy body inclusions. Trichloroethylene (TCE) has been suggested as a potential environmental chemical that may contribute to the development of PD, via conversion to the neurotoxin, 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo). We investigated the effect of an 8 week exposure to TCE or TaClo on wild type and, as an experimental model of PD, A30P mutant α-synuclein overexpressing mice using a combination of behaviour and pathology. TCE or TaClo exposure caused significant DA neuronal loss within the SNpc in both wild type and transgenic mice. Cell numbers were lower in A30P animals than wild type, however, no additive effect of TCE or TaClo exposure and A30P overexpression was found. TCE or TaClo did not appear to lead to acceleration of motor or cognitive deficits in either wild type or A30P mutant mice, potentially because of the modest reductions of DA neuronal number in the SNpc. Our results do however suggest that TCE exposure could be a possible factor in development of PD like changes following exposure


Publication metadata

Author(s): Keane PC, Hanson PS, Patterson L, Blain PG, Hepplewhite P, Khundakar AA, Judge SJ, Kahle PJ, LeBeau FEN, Morris CM

Publication type: Article

Publication status: Published

Journal: Neuroscience Letters

Year: 2019

Volume: 711

Print publication date: 15/10/2019

Online publication date: 15/08/2019

Acceptance date: 14/08/2019

Date deposited: 03/09/2019

ISSN (print): 0304-3940

ISSN (electronic): 1872-7972

Publisher: Elsevier

URL: https://doi.org/10.1016/j.neulet.2019.134437

DOI: 10.1016/j.neulet.2019.134437

PubMed id: 31422098


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