Table 1.
Exercise effects on the nigrostriatal DA system in animal models of PD.
| Study | Animal model | Exercise type | Exercise start timing | Treadmill speed or other parameters | Exercise duration min/day | Total days of exercise | Effect on nigral DA neurons | Effect on striatal DA axons | Effect on striatal DA content | Effect on striatal TH content |
|---|---|---|---|---|---|---|---|---|---|---|
| POSITIVE RESULTS | ||||||||||
| Tillerson et al., 2001 | Rat 6OHDA | Forced limb use | 24 h after 6-OHDA lesion | Not applicable | Up to 28 days | Reduces DA neuron loss | Reduces DA axon loss | Up | Up | |
| Tillerson et al., 2002 | Rat 6OHDA | Forced limb use | 24 h after 6-OHDA lesion | Not applicable | Up to 28 days | Reduces DA neuron loss | Reduces DA axon loss | Up | Up | |
| Cohen et al., 2003 | Rat 6OHDA | Forced limb use | 24 h after 6-OHDA lesion | Not applicable | Up to 28 days | Reduces DA neuron loss | Reduces DA axon loss | Up | Up | |
| Tillerson et al., 2003 | Rat 6OHDA | Treadmill | 24 h after 6-OHDA lesion | 15 m/min | 30 min/day | Up to 28 days | Reduces DA neuron loss | Reduces DA axon loss | Up | Up |
| Yoon et al., 2007 | Rat 6-OHDA | Treadmill | 1 day after 6-OHDA lesion | At a speed of 2 m/min for the first 5 min, and then 3 m/min for the last 25 min | 30 min/days | 14 consecutive days | DA neurons↑ | DA axons↑ | Up | |
| Gerecke et al., 2010 | Mouse MPTP | Running wheel | 3 month prior to MPTP administration | 4.8 km/days | 90 days | Reduces DA neuron loss | Up | Up | ||
| Lau et al., 2011 | Mouse MPTP | Treadmill | For 1 week before, 5 weeks during, and 12 weeks after the completion of chronic MPTP treatment | 5 min at 6 m/min, 5 min at 9 m/min, 20 min at 12 m/min, 5 min at 15 m/min, and 5 min at 12 m/min | 40 min/day, 5 days/week | 18 weeks | Reduces DA neuron loss | Up | Up | |
| Tajiri et al., 2010 | Rat 6OHDA | Treadmill | 24 h after the 6-OHDA lesion | 11 m/min | 5 days/week, 30 min/day | 4 weeks (20 days) | Reduces DA neuron loss | |||
| Tuon et al., 2012 | Rat 6OHDA | Treadmill | 8 weeks pre-6-OHDA lesion | 13–17 m/min | 3 or 4 days/week, 50 min/48h | 8 weeks | Not determined | ND | ND | Up |
| Sung et al., 2012 | Mouse MPTP | Treadmill | 1 day after last MPTP lesion | 12 m /min | 30 min/day, 5 days/week | 4 weeks | Up | Up | ||
| Real et al., 2013 | Rat 6OHDA | Treadmill | 1 month, before 6-OHDA | 3 days/week | DA neurons↑ | |||||
| Goes et al., 2014 | Mouse 6OHDA | Swimming exercise | 4 days after 6-OHDA | 2% body weight were attached to the tails | 5 times /week | 4 weeks | Up | |||
| Smeyne et al., 2015 | Mouse MPTP | Running wheel | 3 months pre MPTP lesion | 3 months | Reduces DA neuron loss | Up | ||||
| Tsou et al., 2015 | Rat MPP+ | Treadmill | 4 weeks prior to 1-methyl-4- phenylpyridine lesion | 12–15 m/min | 60 min/day, 5 days/week | 4 weeks | Reduces DA neuron loss | Up | ||
| Aguiar et al., 2016a | Mouse 6-OHDA | Treadmill | 48 h prior to 6-OHDA lesion | At 16 m/min and speed increased 2 m/min every 3 min until mouse exhaustion | 5 times/week | 6 weeks | Reduces DA neuron loss | DA axons↑ | ||
| Jang et al., 2017 | Mouse MPTP | Treadmill | After MPTP lesion | 10 m/min | 60 min/day, 5 days/week | 8 weeks | Up | Up | Up | |
| Koo et al., 2017b | Mouse MPTP | Treadmill | After MPTP lesion | 10 m/mine | 60 min/day, 5 days/week | 8 weeks | Up | Up | Up | |
| Koo et al., 2017a | Mouse MPTP | Treadmill | After MPTP lesion | 10 m/min | 60 min/day, 5 days/week | 8 weeks | Up | Up | Up | |
| Garcia et al., 2017 | Rat 6OHDA | Treadmill | 1 month, before 6-OHDA | 10 m/min, 40 min | 3 days/week | 1 month | Up | Up | Up | |
| Real et al., 2017 | Rat 6OHDA | Treadmill | 1 month, before 6-OHDA | 10 m/min, 40 min | 3 days/week | 1 month | Up | Up | Up | |
| Shi et al., 2017 | Rat 6OHDA | Treadmill | 24 h post 6-OHDA lesion | 11 m/min | 30 min/day/, 5 days/week, 4 weeks | 4 weeks (20 days) | Reduces DA neuron loss | Reduces DA axon loss | Up | |
| NEGATIVE RESULTS | ||||||||||
| O'Dell et al., 2007 | Rat 6OHDA | Voluntary +forced wheel running | 2.5 weeks before 6-OHDA lesion and continued for up to 4 weeks post-lesion (initiated 1 day after lesion | Forced running: 10.5 m/min | 2 × 30 min/day | 35 days | No effect | |||
| Petzinger et al., 2007 | Mouse MPTP | Treadmill | Started 5 days after MPTP lesion | 9.2 ± 1.1 m/min during the first week that further increased to 20.5 ± 0.7 m/min in the last week | 5 days/week | 28 days | No effect | No effect | No effect | |
| Gorton et al., 2010 | Mouse MPTP | Treadmill (inclined 5)+ running wheels | Started 5 days after MPTP lesion | 6.7 m/min for 30 min-8.5 m/min for 60 min (Treadmill) | 30–60 min/day (Treadmill) | 30 days | No effect | |||
| VanLeeuwen et al., 2010 | Mouse MPTP | Treadmill | Started 5 days after MPTP lesion | 9.2 ± 1.1 m/min- 20.5 ± 0.7 m/min | From 30 min/day 2 sessions of 30 min/day; 5 days/week | 28 days | No effect | |||
| Kintz et al., 2013 | Mouse MPTP | Treadmill | Started 5 days after MPTP lesion | 10.0–24.0 m/min | 2 × 30 min/day, 5 days/week | 28 days | No effect | |||
| Aguiar et al., 2014 | Mouse MPTP | Running wheels | Started 6 weeks prior to MPTP lesion | 6 weeks | No effect | |||||
| Toy et al., 2014 | Mouse MPTP | Treadmill | Started 5 days after MPTP lesion | 10.0–24.0 m/min | 2 × 30 min/day, 5 days/week | 6 weeks | No effect | |||
| Sconce et al., 2015 | Mouse MPTP | Running wheels | 2 weeks after the last dose of MPTP | Not determined | 4 weeks | No effect | ||||
| Aguiar et al., 2016b | Mouse MPTP | Treadmill | 6 week plus 48 h prior to MPTP administration | 11.4 m/min for 25, 30, and 45 min during first three weeks and 13.5 m/min for 25, 30, and 45 min during last three weeks | 5 times/week | 6 weeks | No effect | No effect | No effect | |
| Hood et al., 2016 | Mouse MPTP | Treadmill | 3 weeks after the last dose of MPTP | 10.8 m/min | 60 min/day, 5 days/week | 4 weeks | No change | No effect | No effect | |
| Churchill et al., 2017 | Mouse MPTP | Treadmill | 4-week progressive MPTP, after last dose of MPTP | 18 cm/s | 60 min/day, 5 days/week | 4 weeks | No significant recovery | No significant recovery | No significant recovery | |