Table A.16.

Quantitative understanding of the KER

DA neurons degeneration	Parkinsonian motor symptoms	Treatment	References
15% DA neuronal loss (Nissl staining and TH immunostaining) in SNpc	Mixed pattern of motor impairment observed for testing posture and speed but not for mobility (approx. 3 times the control, as average for total score‐from Figure A.5)	Young adult Sprague‐Dawley rats (2 months old) i.p. injected with PQ 10 mg/kg, twice a week for 4 weeks	Cicchetti et al. (2005)
Decrease in SN dopaminergic neurons of 36% and 61%, respectively (assessed by Fluoro‐gold prelabelling method) Decline in striatal dopamine nerve terminal density of 87% and 94%, respectively (assessed by TH immunoreactivity)	Neurobehavioural syndrome characterised by reduced ambulatory (locomotor) activity 48 h after final treatment (during the course of 60 min experimental session) observed at both doses (reduction approx. 45% after 60 min. Figure A.5A)	Adult C57 BL/6J mice i.p. injected with PQ 5 and 10 mg/kg, 3 doses separated by 1 week each	Brooks et al. (1999)
Differential immunolocalisation and decreased expression levels of TH in SN (60%), FC (50%) and hippocampus (30%) (only measured at 10 mg/kg) Decrease in TH+ and FOX3+ neurons in SN (stereological count) of approximately 40% at 10 mg/kg and of approximately 10–15% at 5 mg/kg	Motor dysfunction (only observed at 10 mg/kg) after 2 weeks of treatment (progressive over the next days) with severe postural instability and gait impairment consistent with a unilateral lesion: Curling test (qualitative asymmetry evaluation): ipsilateral Gait impairment: walking footprint pathway (qualitative assessment), stride length of consecutive steps and step frequency	Adult male Swiss Albino mice i.p. treated with 5 and 10 mg/kg PQ twice a week for 4 weeks	Mitra et al. (2011)
Dose‐dependent DA depletion in ipsilateral striatum 2 weeks after treatment. 26. 7, 60.3 and 91.5% at 1, 2 and 3 μg PQ respectively. The effect lasted up to 16 weeks Marked loss of Nissl substances and severe loss of neurons at 3 μg PQ (2 weeks after injection). The effect was considered moderate at 2 μg PQ (2 weeks after injection)	Circling behaviour (direction of the lesioned side) due to the imbalance of dopaminergic activity in striata (unilateral lesion) at 3 μg PQ Dose‐dependent rotational behaviour in rats contralateral to the lesion side in response to apomorphine s.c. administration 0.5 mg/kg (inducing circling behaviour) at 3 μg PQ (2 weeks after injection)	Intracerebral (unilateral intranigral) injection of 1, 2 and 3 μg PQ in male Wistar rats for 16 weeks	Liou et al. (1996)
Progressive TH positive neurons (stereology count) loss up to 47% at the end of week 8 post PQ exposure	Deficiency in behavioural motor function (horizontal beam walking test) after 4 and 8 weeks	Long Evans Hooded rats i.p. injected PQ 10 mg/kg bw, every 5 days over 20 days	Muthukumaran et al. (2014)
Nigrostriatal dopaminergic neurons reduced in all age groups but progressive in 18‐month‐old PQ groups between 2 weeks and 3 months post‐exposure	Reduction in locomotor activity and motor coordination, age dependent with 18‐month old mice most affected and failing to recover 24 h post treatment	Male C57BL/6 mice (6 weeks, 5 months and 18 months old) i.p. treated with PQ 10 mg/kg twice a week for 3 weeks (6 injections in total)	Thiruchelvam et al. (2003)