EXERCISE IN AN ANIMAL MODEL OF PARKINSON'S DISEASE: MOTOR RECOVERY BUT NOT RESTORATION OF THE NIGROSTRIATAL PATHWAY
EXERCISE IN AN ANIMAL MODEL OF PARKINSON'S DISEASE: MOTOR RECOVERY BUT NOT RESTORATION OF THE NIGROSTRIATAL PATHWAY
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DOI：
10.1016/j.neuroscience.2017.07.031
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发表时间：
2017-09-17
期刊：
影响因子：
3.3
通讯作者：
Meshul, C. K.
中科院分区：
文献类型：
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作者：
Churchill, M. J.;Pflibsen, L.;Meshul, C. K.
许多临床研究报告了运动疗法对帕金森病 (PD) 患者的益处。运动不能阻止帕金森病的进展或促进黑质致密部 (SNpc) 中多巴胺 (DA) 神经元的恢复 (Bega et al., 2014)。为了解决这个悖论，我们使用了渐进式 MPTP（1-甲基1-4-苯基-1,2,3,6-四氢吡啶）小鼠模型，在完成毒素施用（即恢复）后，我们开始进行 4 周的跑步机运动。我们发现，在 MPTP/运动 (MPTP + EX) 组中，与仅使用 MPTP 的组相比，多项步态功能指标均得到恢复。尽管 SNpc 和纹状体末端的酪氨酸羟化酶 (TH) 阳性 DA 神经元有小幅恢复，但这种增加并不具有统计学意义。 TH 的这些微小变化并不能解释运动功能的改善。 MPTP 组纹状体中糖基化/非糖基化多巴胺转运蛋白 (DAT) 显着增加 170%，小胶质细胞标记物 IBA-1 显着增加 200%。 MPTP + EX 组显示这些标记几乎完全恢复到车辆水平。运动导致纹状体中 GLT-1 水平增加，但纹状体 BDNF 蛋白表达没有变化。我们的数据表明，运动恢复并不是由 DA 神经元或末梢的任何显着恢复引起的，而是由 DAT 的恢复和抑制炎症反应引起的。虽然运动不能促进黑质纹状体 DA 的恢复，但应与控制 PD 症状的药物方法结合使用。由 Elsevier Ltd 代表 IBRO 出版。
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-methy1-4-phenyl-1,2,3,6-tetra-hydropyridine) mouse model in which we initiated 4 weeks 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 glycosylatedj 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. Published by Elsevier Ltd on behalf of IBRO.