Determination of reactive oxygen species associated with the degeneration of dopaminergic neurons during dopamine metabolism
Determination of reactive oxygen species associated with the degeneration of dopaminergic neurons during dopamine metabolism
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DOI：
10.3109/10715760903456084
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发表时间：
2010-01
影响因子：
3.3
通讯作者：
M. Yamato;Wataru Kudo;Takeshi Shiba;Ken‐ichi Yamada;Toshiaki Watanabe;H. Utsumi
中科院分区：
文献类型：
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作者：
M. Yamato;Wataru Kudo;Takeshi Shiba;Ken‐ichi Yamada;Toshiaki Watanabe;H. Utsumi
摘要氧化应激被认为是多巴胺引起神经元损伤的重要机制。这项研究提供了X波段电子自旋共振(ESR)光谱证据，证明了多巴胺代谢过程中活性氧物种(ROS)的产生。作者通过使用微透析将小鼠纹状体浸泡在含有酪胺的灌流液中，诱导了小鼠纹状体中过量的多巴胺代谢。在灌流液中加入酪胺可显著提高细胞外多巴胺和过氧化氢的水平。羟基-TEMPO的ESR信号在酪胺灌流期间衰减，用单胺氧化酶抑制剂或自由基清除剂处理可抑制该信号的衰减。观察到酪氨酸羟基酶免疫阳性纤维数量和多巴胺浓度在酪胺灌流后减少。此外，酪胺灌流的小鼠表现出明显的甲基苯丙胺诱导的旋转反应。值得注意的是，酪胺的这些作用被同时灌流羟基-TEMPO所抑制。这些结果表明，在羟基-TEMPO的监测下，ROS的产生对多巴胺能神经元造成了氧化损伤。
Abstract Oxidative stress is believed to be an important mechanism underlying dopamine-induced neuronal damage. This study provides X-band electron spin resonance (ESR) spectroscopic evidence for reactive oxygen species (ROS) generation during dopamine metabolism. The authors induced excess dopamine metabolism in the mouse striatum by bathing it in tyramine-containing perfusate using microdialysis. The addition of tyramine to the perfusate raised the levels of extracellular dopamine and hydrogen peroxide significantly. The ESR signal from hydroxy-TEMPO decayed during tyramine perfusion and treatment with a monoamine-oxidase inhibitor or radical scavenger suppressed the signal decay. Decreases in the number of tyrosine hydroxylase-immunopositive fibres and in dopamine concentration after tyramine perfusion were observed. Moreover, the tyramine-perfused mice showed a marked methamphetamine-induced rotational response. Notably, these effects of tyramine were suppressed by the simultaneous perfusion of hydroxy-TEMPO. These findings indicate that the ROS generation, which was monitored by hydroxy-TEMPO, caused oxidative damage to the dopaminergic neurons.