Lacombe Emilie, Khaindrava Vitaly, Melon Christophe, Oueslati Abid, Kerkerian-Le Goff Lydia, Salin Pascal
Team Cellular Interactions, Neurodegeneration and Neuroplasticity, Developmental Biology Institute of Marseille-Luminy, UMR 6216 CNRS-Université de Méditerranée, Marseille, France.
Neurobiol Dis. 2009 Oct;36(1):116-25. doi: 10.1016/j.nbd.2009.07.002. Epub 2009 Jul 15.
Subthalamic nucleus high frequency stimulation (STN-HFS) efficiently alleviates L-DOPA-sensitive parkinsonian motor symptoms, but has no direct beneficial action on L-DOPA-induced dyskinesias (LID). Here, we provide evidence that anti-akinetic STN-HFS or dyskinesiogenic L-DOPA similarly reversed the dopamine lesion-induced increases in gene expression of cytochrome oxidase subunit I (CoI), a metabolic marker of neuronal activity, in the globus pallidus, STN and substantia nigra pars reticulata (SNr) in rats. In contrast, in entopeduncular nucleus (EP), STN-HFS did not modify the lesion-induced increase in CoI mRNA levels, whereas L-DOPA induced a marked decrease versus control. Combining the two treatments did not reveal significant interaction. Interestingly, CoI gene expression in EP but not in SNr was inversely correlated with striatal preprodynorphin mRNA level, a LID marker. This work suggests the existence of two functional basal ganglia subcircuits: the one, including STN and SNr, involved in antiparkinsonian action, and the other, including EP, preferentially involved in LID.
丘脑底核高频刺激（STN-HFS）能有效缓解左旋多巴敏感的帕金森运动症状，但对左旋多巴诱发的异动症（LID）没有直接的有益作用。在此，我们提供证据表明，抗运动不能的STN-HFS或致异动症的左旋多巴同样能逆转多巴胺损伤诱导的大鼠苍白球、丘脑底核和黑质网状部（SNr）中细胞色素氧化酶亚基I（CoI）基因表达增加，CoI是神经元活动的代谢标志物。相比之下，在内侧苍白球（EP）中，STN-HFS并未改变损伤诱导的CoI mRNA水平升高，而左旋多巴与对照组相比则诱导了显著降低。联合两种治疗未发现显著的相互作用。有趣的是，EP而非SNr中的CoI基因表达与纹状体前强啡肽原mRNA水平呈负相关，前强啡肽原mRNA水平是LID的标志物。这项研究表明存在两个功能性基底神经节子回路：一个包括丘脑底核和黑质网状部，参与抗帕金森作用；另一个包括内侧苍白球，优先参与左旋多巴诱发的异动症。
