Characterisation of a novel model of Parkinson's disease by intra-striatal infusion of the pesticide rotenone

Differential pattern of motor impairments in neurotoxic, environmental and inflammation-driven rat models of Parkinson’s disease

“…Since Parkinson's disease is an age-progressive neurodegenerative disease, a progressive onset of motor dysfunction is another highly desirable feature of Parkinson's disease models. In line with previous reports, this is evidently not a feature of any of these acute lesion models (at least at the lesion regime using in the current study) (Kirik et al, 1998, Grealish et al, 2008, Mulcahy et al, 2011, Hoban et al, 2013, and this should be borne in mind as a limitation of all of these models.…”

“…They were then performance-matched to receive unilateral, 4 site, intra-striatal infusion of 6-OHDA (4 x 7 μg; n=8), LPS (4 x 5 μg; n=8) or rotenone (4 x 0.9 μg; n=8). Doses were chosen to induce a similar level of nigrostriatal neurodegeneration based on our previous studies (Mulcahy et al, 2011, Hoban et al, 2013. Behavioural testing resumed the day after lesion surgery and continued for 10 weeks during which time amphetamine-induced rotation was also assessed (at 3 weeks post-lesion).…”

“…Extracted brains were then post-fixed in 4% paraformaldehyde overnight and cyroprotected in 25% sucrose plus 0.1% sodium azide solution. Serial coronal sections (30 μm) were cut using a freezing stage sledge microtome, and a 1:6 series of sections was used for all quantitative immunohistochemistry as previously described (Mulcahy et al, 2011, Hoban et al, 2013. In brief, endogenous peroxidise activity was quenched using a solution of 3% hydrogen peroxide/10% methanol in distilled water.…”

“…However, systemic rotenone is associated with significant systemic organ toxicity (Ferrante et al, 1997, Lapointe et al, 2004, body weight loss Schmidt, 2004, Greene et al, 2009), and mortality rates of up to 50% (Ferrante et al, 1997, Antkiewicz-Michaluk et al, 2003, while systemic LPS has also been associated with 'sickness behaviour' (Hart, 1988). Therefore, for these reasons, models have also been developed in which rotenone (Mulcahy et al, 2011, Mulcahy et al, 2012 or LPS (Hoban et al, 2013) are injected directly into the rat nigrostriatal pathway.…”

Molecular and Neurochemical Mechanisms Dopamine Oxidation To O-Quinones in Parkinson’s Disease Pathogenesis

“…The entire experimental model for Parkinson's disease used exogenous neurotoxins such as 6-hydroxydopamine [111], MPTP [112], paraquat [113], rotenone [114] and dithiocarbamates [115]. Most likely, the degeneration of dopaminergic neurons containing neuromelanin is primarily dependent on an endogenous neurotoxin(s), such as (i) the o-quinones (dopamine o-quinone, aminochrome and 5,6-indolequinone) generated during dopamine oxidation; (ii) 3,4-dihydroxyphenylacetaldehyde generated by the oxidative deamination of dopamine catalyzed by MAO [116]; (iii) salsolinol, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, the condensation product of dopamine with aldehyde [86].…”