Paul Keane

PhD Student

Introduction and area of work:

My project will aim to determine if there is any link between exposure to the industrial solvent trichloroethylene (TCE) and Parkinson’s disease, and, if so, what the mechanism of this toxicity is.

There is gathering evidence that TCE is linked with Parkinson’s disease. It has been noticed that a number of Parkinson’s sufferers have worked in close proximity to TCE and further investigations have shown that others who work in the same areas are showing early signs of the disease. It has also been shown that one of the metabolites of TCE, TaClo, can be formed from TCE via choral in man and has neurotoxic properties in dopaminergic neurons in both in vitro studies and animal models.

Qualifications:

- B.Sc. (Hons) in Pharmacology from Manchester University

Techniques:

In vitro models of TCE exposure will be developed based on the previous exposure paradigm that has been developed. We will utilise both tumour and stem cell approaches to understand toxic mechanisms of TCE exposure. Cell viability assays in the presence of specific inhibitors or gene transfection studies along with immunocytochemistry and western blotting will be used to characterise the pathways leading to cell death.

The metabolism and pharmacokinetics of TCE and the production of TCE metabolites will be studied in vivo. Animals will be dosed and at set time points blood and terminal tissues sampled. TCE and its metabolites will be identified using LC-MS/MS. This will provide us with information on the likely exposure levels that could be attained in vivo in man.

To establish if TCE exposure causes motor impairment in exposed animals, longitudinal assessment of motor function will be undertaken using a variety of measures.
Determination of pathology in the SN of exposed animals will be used and will utilise stereological analysis of neurone and glial numbers in paraffin sections of brain.