PLoS Genet：揭示调节大脑多巴胺水平的机制 或帮助开发治疗帕金森疾病的新型疗法

      近日，发表于国际杂志PLoS Genetics上的一篇研究报告中，来自蒙特利尔临床研究学院的研究人员通过对患早期帕金森疾病的小鼠模型进行研究揭示了调节大脑中多巴胺水平的机制。

      利用基因表达谱技术来测定成千上万个基因的活性，研究人员就可以调查中脑中的多巴胺能神经元，多巴胺能神经元可以利用多巴胺来发送信号至别的神经细胞中，而这些神经元在帕金森患者机体中被认为可以发生退化。
      研究者Drouin博士指出，我们在多巴胺能神经元中发现基因Rgs6的表达会被限制，此前研究发现该基因可以通过一种名为Pitx3的转录因子来实现自我控制，而且Pitx3在多巴胺能神经元的存活中扮演着重要角色。
      通过这项研究，研究人员发现，Rgs6基因的缺陷会引发多巴胺能神经元死亡，具体来讲就是，当移除Rgs6基因后，其就可以解除对过量多巴胺信号的抑制，过量的游离多巴胺信号的积累就会引发细胞压力效应，从而引发神经元死亡；当前的研究揭示，基因Rgs6或许是一种开发治疗帕金森疾病的新型药物靶点。
      据加拿大帕金森协会数据显示，在加拿大有大约10万帕金森患者，这种进行性的神经变性疾病最初会影响个体的自由控制运动，这往往是由于机体中产生多巴胺的细胞的缺失而引发的，而多巴胺正扮演了一个信使在不同的脑细胞之间来回穿梭，控制机体的运动。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Rgs6 is Required for Adult Maintenance of Dopaminergic Neurons in the Ventral Substantia Nigra
PLoS Genetics  doi:10.1371/journal.pgen.1004863
Bifsha P, Yang J, Fisher RA, Drouin J 
Parkinson disease (PD) is characterized by the preferential, but poorly understood, vulnerability to degeneration of midbrain dopaminergic (mDA) neurons in the ventral substantia nigra compacta (vSNc). These sensitive mDA neurons express Pitx3, a transcription factor that is critical for their survival during development. We used this dependence to identify, by flow cytometry and expression profiling, the negative regulator of G-protein signaling Rgs6 for its restricted expression in these neurons. In contrast to Pitx3−/− mDA neurons that die during fetal (vSNc) or post-natal (VTA) period, the vSNc mDA neurons of Rgs6−/− mutant mice begin to exhibit unilateral signs of degeneration at around 6 months of age, and by one year cell loss is observed in a fraction of mice. Unilateral cell loss is accompanied by contralateral degenerating neurons that exhibit smaller cell size, altered morphology and reduced dendritic network. The degenerating neurons have low levels of tyrosine hydroxylase (TH) and decreased nuclear Pitx3; accordingly, expression of many Pitx3 target gene products is altered, including Vmat2, Bdnf, Aldh1a1 (Adh2) and Fgf10. These low TH neurons also express markers of increased dopamine signaling, namely increased DAT and phospho-Erk1/2 expression. The late onset degeneration may reflect the protective action of Rgs6 against excessive DA signaling throughout life. Rgs6-dependent protection is thus critical for adult survival and maintenance of the vSNc mDA neurons that are most affected in PD.