Arnold Jennifer C, Salvatore Michael F
Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center , Shreveport, Louisiana 71130, United States.
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center , Fort Worth, Texas 76107, United States.
ACS Chem Neurosci. 2016 Feb 17;7(2):227-39. doi: 10.1021/acschemneuro.5b00282. Epub 2015 Dec 8.
Exercise may alleviate locomotor impairment in Parkinson's disease (PD) or aging. Identifying molecular responses immediately engaged by exercise in the nigrostriatal pathway and allied tissue may reveal critical targets associated with its long-term benefits. In aging, there is loss of tyrosine hydroxylase (TH) and the glial cell line-derived neurotrophic factor (GDNF) receptor, GFR-α1, in the substantia nigra (SN). Exercise can increase GDNF expression, but its effect on GFR-α1 expression is unknown. Infusion of GDNF into striatum or GFR-α1 in SN, respectively, can increase locomotor activity and TH function in SN but not striatum in aged rats. GDNF may also increase glutamate transporter expression, which attenuates TH loss in PD models. We utilized a footshock-free treadmill exercise regimen to determine the immediate impact of short-term exercise on GFR-α1 expression, dopamine regulation, glutamate transporter expression, and glutamate uptake in 18 month old male Brown-Norway/Fischer 344 F1 hybrid rats. GFR-α1 and TH expression significantly increased in SN but not striatum. This exercise regimen did not affect glutamate uptake or glutamate transporter expression in striatum. However, EAAC1 expression increased in SN. These results indicate that nigral GFR-α1 and EAAC1 expression increased in conjunction with increased nigral TH expression following short-term exercise.
运动可能会减轻帕金森病（PD）或衰老过程中的运动功能障碍。确定运动在黑质纹状体通路及相关组织中立即引发的分子反应，可能会揭示与其长期益处相关的关键靶点。在衰老过程中，黑质（SN）中酪氨酸羟化酶（TH）和胶质细胞源性神经营养因子（GDNF）受体GFR-α1会减少。运动可以增加GDNF的表达，但其对GFR-α1表达的影响尚不清楚。分别向老年大鼠的纹状体中注入GDNF或向黑质中注入GFR-α1，可以增加其运动活性以及黑质而非纹状体中的TH功能。GDNF还可能增加谷氨酸转运体的表达，从而减轻PD模型中TH的损失。我们采用无足部电击的跑步机运动方案，来确定短期运动对18月龄雄性布朗-挪威/费希尔344 F1杂交大鼠的GFR-α1表达、多巴胺调节、谷氨酸转运体表达和谷氨酸摄取的即时影响。黑质中GFR-α1和TH的表达显著增加，但纹状体中没有。这种运动方案不影响纹状体中的谷氨酸摄取或谷氨酸转运体表达。然而，黑质中EAAC1的表达增加了。这些结果表明短期运动后，黑质中GFR-α1和EAAC1的表达随着黑质中TH表达增加而增加。
