PLoS ONE：调控生物钟成精神分裂症治疗关键

癫痫是心境障碍的除此以外临床表现，是躁狂高烧和抑郁高烧在同一患者身上愈演愈烈的性疾病，以躁狂和抑郁交替高烧特点的性疾病。临床主要表现除此以外心境或情感显著而无疑的改变，以情感低落或助长（可伴或不伴焦虑），伴有相应的主体商业活动水平（思维和不当）的改变，间隙期精神状态基本正常，有反复高烧的倾向。在世界上首都区的1％至3％受到此种性疾病的困扰。

癫痫极端的情绪波动与连续不断的里断有密切关系，连续不断指控制我们身体时计的24小时节律，调控我们的昼夜商业活动。

在过去的60多年里，铋卤（氯化铋）一直是治疗癫痫的里流砥柱，但早期进行一些深入研究一直试图解决问题铋卤确实以及如何对大脑及机体做梦显现出直接影响。

生命科学学院首席深入研究员Qing-Jun Meng说，我们的深入研究表明铋有一个取而代之、有效的效用，即能增加时计节律的幅度或准确度，说明了了铋与情绪保持稳定、癫痫和做梦二者之间的关联适度。

通过一个极其重要时计酶的动态变化，我们发现铋通过阻断乳酸合酶转移酶或GSK3酶，能三倍增加线粒体生物时计的准确度。

我们的发现之所以很极其重要主要有两个原因：首先，该深入研究为铋是如何能用来保持稳定癫痫患者的情绪波动提供了一种取而代之解释；其次，深入研究提供了技术开发取而代之抗癫痫类固醇取而代之思路，新类固醇可能效仿或甚至提高铋对GSK3的效用，同时并不会显现出因使用铋卤所随之而来的副效用。

铋卤的副效用以外烦躁、痤疮、口渴、神经无力、震颤、镇静等。目前，抑制GSK3的类固醇已在深入研究技术开发，因为GSK3已被验证在其他性疾病以外白血病和阿尔茨海默氏病里充分发挥极其重要效用。 Meng药剂师补充说：除了GSK3外，铋卤具在线粒体有最常的效用位点。单单阻断GSK3的类固醇将能提高铋的“脱靶现象”，具有独特的竞争者。

我们的深入研究已经确定了抑制GSK3后能强适度的推动可调消化系统时计节律的效用，因此技术的发展该机制技术开发出一种取而代之类固醇来可调做梦是很有可能的。我们所开展的深入研究也可能造成显现出治疗癫痫的新方法，但这一点还需要进行相应的试验里。

该深入研究由生物医学委员会和生物新科技和生物科学深入研究委员会（BBSRC）捐献，并公开发表在PLoS One上。（生物谷：Bioon）

doi:10.1371/journal.pone.0033292PMC:PMID:

Lithium Impacts on the Amplitude and Period of the Molecular Circadian Clockwork.

Jian Li, Wei-Qun Lu, Stephen Beesley, Andrew S. I. Loudon, Qing-Jun Meng.

Lithium salt has been widely used in treatment of Bipolar Disorder, a mental disturbance associated with circadian rhythm disruptions. Lithium mildly but consistently lengthens circadian period of behioural rhythms in multiple organisms. To systematically address the impacts of lithium on circadian pacemaking and the underlying mechanisms, we measured locomotor activity in mice in vivo following chronic lithium treatment, and also tracked clock protein dynamics (PER2::Luciferase) in vitro in lithium-treated tissue slices/cells. Lithium lengthens period of both the locomotor activity rhythms, as well as the molecular oscillations in the suprachiasmatic nucleus, lung tissues and fibroblast cells. In addition, we also identified significantly elevated PER2::LUC expression and oscillation amplitude in both central and peripheral pacemakers. Elevation of PER2::LUC by lithium was not associated with changes in protein stabilities of PER2, but instead with increased transcription of Per2 gene. Although lithium and GSK3 inhibition showed opposing effects on clock period, they acted in a similar fashion to up-regulate PER2 expression and oscillation amplitude. Collectively, our data he identified a novel amplitude-enhancing effect of lithium on the PER2 protein rhythms in the central and peripheral circadian clockwork, which may involve a GSK3-mediated signalling pathway. These findings may advance our understanding of the therapeutic actions of lithium in Bipolar Disorder or other psychiatric diseases that involve circadian rhythm disruptions.