Exercise in an animal model of Parkinson’s disease: Motor recovery but not restoration of the nigrostriatal pathway

•Exercise causes motor recovery in a progressive MPTP animal model of PD.•Motor recovery is not facilitated by restoration of dopamine within the nigrostriatal pathway.•Dopamine transporter levels were recovered in the MPTP animals treated with exercise suggesting a role in motor recovery.•Inflammat...

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Veröffentlicht in:Neuroscience 2017-09, Vol.359, p.224-247
Hauptverfasser: Churchill, M.J., Pflibsen, L., Sconce, M.D., Moore, C., Kim, K., Meshul, C.K.
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Sprache:eng
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Zusammenfassung:•Exercise causes motor recovery in a progressive MPTP animal model of PD.•Motor recovery is not facilitated by restoration of dopamine within the nigrostriatal pathway.•Dopamine transporter levels were recovered in the MPTP animals treated with exercise suggesting a role in motor recovery.•Inflammatory proteins were lowered in the exercised MPTP animals compared to the MPTP only groups.•Glutamate transporters were increased following exercise suggesting increased recycling of extracellular glutamate. Many clinical studies have reported on the benefits of exercise therapy in patients with Parkinson's disease (PD). Exercise cannot stop the progression of PD or facilitate the recovery of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) (Bega et al., 2014). To tease apart this paradox, we utilized a progressive MPTP (1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine) mouse model in which we initiated 4weeks of treadmill exercise after the completion of toxin administration (i.e., restoration). We found in our MPTP/exercise (MPTP+EX) group several measures of gait function that recovered compared to the MPTP only group. Although there was a small recovery of tyrosine hydroxylase (TH) positive DA neurons in the SNpc and terminals in the striatum, this increase was not statistically significant. These small changes in TH could not explain the improvement of motor function. The MPTP group had a significant 170% increase in the glycosylated/non-glycosylated dopamine transporter (DAT) and a 200% increase in microglial marker, IBA-1, in the striatum. The MPTP+EX group showed a nearly full recovery of these markers back to the vehicle levels. There was an increase in GLT-1 levels in the striatum due to exercise, with no change in striatal BDNF protein expression. Our data suggest that motor recovery was not prompted by any significant restoration of DA neurons or terminals, but rather the recovery of DAT and dampening the inflammatory response. Although exercise does not promote recovery of nigrostriatal DA, it should be used in conjunction with pharmaceutical methods for controlling PD symptoms.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2017.07.031