Bacci Jean-Jacques, Absi El Hadi, Manrique Christine, Baunez Christelle, Salin Pascal, Kerkerian-Le Goff Lydia
Laboratoire Interactions Cellulaires Neurodégénérescence et Neuroplasticité, CNRS, 13402 Marseille Cedex 20, France.
Eur J Neurosci. 2004 Dec;20(12):3331-41. doi: 10.1111/j.1460-9568.2004.03792.x.
This study examined the effects of prolonged (4 days) high frequency stimulation (HFS) of the subthalamic nucleus (STN), in comparison with those of STN lesion, on the dopamine denervation-mediated cellular changes in the basal ganglia in a Wistar rat model of Parkinson's disease. STN HFS counteracted the dopamine lesion-induced increase in GAD67 mRNA expression in the output structures of the basal ganglia, as shown previously after STN lesion, providing cellular support for the similar antiparkinsonian benefits produced by the two surgical procedures. The dopamine denervation-induced increase in GAD67 mRNA levels in the globus pallidus was partially antagonized after HFS and totally reversed after ibotenate-induced STN lesion. The overexpression of striatal enkephalin mRNA tended to be further increased by HFS but was antagonized by STN lesion. The decrease in striatal substance P mRNA levels was affected neither by STN HFS nor lesion. As STN HFS for two hours was previously found not to interfere with the effects of dopamine lesion in the globus pallidus and striatum, the present data provide strong evidence that the effects of STN surgery in these structures involve long-term adaptive processes and that the rearrangements mediated by HFS and lesion are, at least in part, different.
本研究在帕金森病的Wistar大鼠模型中，将丘脑底核（STN）的长时间（4天）高频刺激（HFS）与STN毁损的效应相比较，研究其对多巴胺去神经支配介导的基底神经节细胞变化的影响。如先前在STN毁损后所显示的那样，STN HFS抵消了基底神经节输出结构中多巴胺损伤诱导的GAD67 mRNA表达增加，为两种手术方法产生的类似抗帕金森病益处提供了细胞支持。苍白球中多巴胺去神经支配诱导的GAD67 mRNA水平增加在HFS后部分被拮抗，在鹅膏蕈氨酸诱导的STN毁损后完全逆转。纹状体脑啡肽mRNA的过表达倾向于因HFS而进一步增加，但被STN毁损所拮抗。纹状体P物质mRNA水平的降低既不受STN HFS影响，也不受毁损影响。由于先前发现两小时的STN HFS不干扰苍白球和纹状体中多巴胺损伤的效应，目前的数据提供了强有力的证据，表明STN手术在这些结构中的效应涉及长期适应性过程，并且由HFS和毁损介导的重排至少部分是不同的。
