PLoS ONE：调控生物钟变成躁郁症治疗关键

躁郁症是心境障碍的都由临床发挥，是躁狂发作和抑郁发作在同一病人身上发生的传染病，以躁狂和抑郁交替发作特点的传染病。临床主要发挥都由心境或情感总体而持久的改变，以情感欠佳或加剧（可伴或不伴焦虑），伴有附加的整体社交活动水平（认知和行为）的改变，间隙期冷漠基本出现异常，有反复发作的倾向。亚太地区常住人口的1％至3％受到此种传染病的困扰。

躁郁症极端的精神状态瞬时与昼夜节律的暂停有紧密联系，昼夜节律常指控制我们身体步进的24小时节律，调控我们的昼夜社交活动。

在过去的60多年中，钴长芦（氯化钴）一直是治疗躁郁症的中流砥柱，但晚期顺利完成一些数据分析一直试图找到钴长芦确实以及如何对脑部及机体做梦激发影响。

材料科学的学院首席数据分析员Qing-Jun Meng说，我们的数据分析表明钴有一个取而代之、必要的起着，即能提高步进节律的倾斜度或切变，揭示了钴与精神状态稳定、躁郁症和做梦之间的关联性。

通过一个关键步进蛋白的动态变化，我们发现钴通过阻断糖类合酶激酶或GSK3酶，能三倍提高线粒体生物步进的切变。

我们的发现之所以很重要主要有两个原因：首先，该数据分析为钴是如何能用来稳定躁郁症病人的精神状态瞬时缺少了一种取而代之解释；其次，数据分析缺少了整合取而代之抗躁郁症用药取而代之思路，新用药或许以此或甚至增强钴对GSK3的起着，同时并不会激发因使用钴长芦所带来的副起着。

钴长芦的副起着以皆恶心、痤疮、口渴、肌肉无力、震颤、镇静等。现阶段，抑制GSK3的用药已在数据分析整合，因为GSK3已被证明在其他传染病以皆糖尿病和阿尔茨海默氏病中发挥重要起着。 Meng医生补充说：除了GSK3皆，钴长芦具在线粒体有广泛应用的起着位点。单单阻断GSK3的用药将能增大钴的“脱靶效应”，具有契合的优势。

我们的数据分析早就断定了抑制GSK3后能强大性的促进调节人体内步进节律的起着，因此应用该程序整合出一种取而代之用药来调节做梦是很有或许的。我们所卓有成效的数据分析也或许导致激发治疗躁郁症的更进一步，但这一点还并不需要顺利完成附加的测试。

该数据分析由医学数据分析理事会和生物技术和生物科学数据分析理事会（BBSRC）资助，并发表在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.