Exercise-Mediated Increase in Nigral Tyrosine Hydroxylase Is Accompanied by Increased Nigral GFR-α1 and EAAC1 Expression in Aging Rats.
Exercise-Mediated Increase in Nigral Tyrosine Hydroxylase Is Accompanied by Increased Nigral GFR-α1 and EAAC1 Expression in Aging Rats.
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DOI：
10.1021/acschemneuro.5b00282
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发表时间：
2016-02-17
影响因子：
5
通讯作者：
Salvatore MF
中科院分区：
文献类型：
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作者：
Arnold JC;Salvatore MF
运动可以缓解帕金森病 (PD) 或衰老引起的运动障碍。识别黑质纹状体通路和相关组织中运动立即引起的分子反应可能会揭示与其长期益处相关的关键目标。在衰老过程中，黑质 (SN) 中的酪氨酸羟化酶 (TH) 和胶质细胞系源性神经营养因子 (GDNF) 受体 GFR-α1 会丧失。运动可以增加GDNF表达，但其对GFR-α1表达的影响尚不清楚。将 GDNF 分别注入纹状体或 SN 中的 GFR-α1 可以增加 SN 中的运动活性和 TH 功能，但不能增加老年大鼠的纹状体。 GDNF 还可能增加谷氨酸转运蛋白的表达，从而减轻 PD 模型中 TH 的损失。我们利用无足部震动的跑步机运动方案来确定短期运动对 18 个月大的雄性 Brown-Norway/Fischer 344 F1 杂交大鼠的 GFR-α1 表达、多巴胺调节、谷氨酸转运蛋白表达和谷氨酸摄取的直接影响。 GFR-α1 和 TH 表达在 SN 中显着增加，但纹状体中没有显着增加。这种运动方案不影响纹状体中谷氨酸的摄取或谷氨酸转运蛋白的表达。然而，SN 中 EAAC1 表达增加。这些结果表明，短期运动后黑质 GFR-α1 和 EAAC1 表达增加，同时黑质 TH 表达增加。
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.