No abstract

Pa ki so s disease (PD) has been linked to a variety of environmental and immunological challenges involving both oxidative and inflammatory processes, however, genetics also clearly plays a role in vulnerability to such insults. Indeed, the Gly-2019-Ser (G2019S) leucine rich repeat kinase (LRRK2) mutation is the most common mutation enriched compared to controls in both familial and sporadic Pa ki so s patie ts. Our current study focuses on the interplay between the G2019S genetic mutation and exposure to the bacterial endotoxin, lipopolysaccharide (LPS). In the current study mice were centrally infused with either vehicle or one of two doses of LPS (2 or 10ug) in order to determine whether an inflammatory based insult would produce augmented pathology in G2019S mutant mice. Infusion of LPS into the substantia nigra pars compacta (SNc; the region containing dopamine neurons which degenerate in PD) produced a (non-statistically significant) trend towards a dose-dependent reduction in

Parkinson's disease (PD) results from the progressive loss of dopamine producing neurons in the Substantia Nigra pars comapcta (SNc). This loss is thought to occur over several years to decades and current evidence suggests that neuroinflammation may play a central role in this loss. Numerous epidemiological studies have implicated chronic exposure to environmental toxicants such as heavy metals and pesticides to risk of developing PD. Indeed, many of these risk factors have been validated as rodent models of PD, able to induce dopaminergic cell loss in the SNc as well as motor dysfunction. While research strongly supports a role for environmental toxicants and inflammation in PD relatively little work has examined the interactions between these toxicants and other risk factors including senescence, genetic vulnerabilities, the gut microbiota or iii This thesis is based upon the following four manuscripts referred to in text by their corresponding chapter numbers.