Fig. 1

An initial study that involved intra-SNc LPS (2 μg) infusion followed by paraquat administration (10 mg/kg; ip) revealed that wild-type (WT) mice displayed signs of extreme sickness, with a significant number (6/9) of mice either died outright or had to be euthanized (owing to moribund presentation) by the ninth injection. In contrast, the mortality rate was reduced in LRRK2 knockout (KO) mice, such that only 1/6 reached end state following the LPS + paraquat regimen. (a) The follow-up study showed that in the absence of LPS and with a reduced paraquat injection regimen, paraquat-treated WT mice still displayed significant (albeit less) pathological signs in terms of ratings of sickness (b, c) and weight loss (d, e) by their sixth paraquat injection. Importantly, once again this effect was prevented by LRRK2 KO (b, d). However, the G2019S (GS-Tg) transgenic mice did not significantly differ from WT animals in terms of either sickness (c) or weight loss (e). Sickness was calculated as a composite score by blind raters including ptosis, piloerection, lethargy, and curled body posture. *p < 0.05, relative to respective controls