PLoS ONE：调控生理成躁郁症治疗关键

帕金森氏症是心态障碍的一组原发性，是躁狂猝死和忧郁症猝死在同一病征脖子起因的癌症，以躁狂和忧郁症断断续续猝死特点的癌症。临床主要平庸一组心态或心灵显著而持久的相反，以心灵低落或高涨（可伴或不伴焦虑），伴有具体来感叹的整体社会活动水平（思维和犯罪行为）的相反，间隙期精神状态基本短时间，有反复猝死的取向。全球总人口的1％至3％受到此种癌症的困扰。

帕金森氏症排外的情绪反转与昼夜脉搏的中断有紧密联系，昼夜脉搏指控制我们身体时计的24小时脉搏，调控我们的昼夜社会活动。

在过去的60多年中，硫醋（氯化硫）仍然是疗法帕金森氏症的引以为傲，但早期进行一些分析仍然试图找出取而代之硫醋否以及如何对大脑及机体心率造成了影响。

生命科学学院首席分析员Qing-Jun Meng感叹，我们的分析证明硫有一个最初、有效的发挥作用，即能减低时计脉搏的稍微或强度，揭示了硫与情绪稳定、帕金森氏症和心率相互间的关连性。

通过一个关键时计防原的动态变化，我们发现硫通过堵塞糖原合酵素激酵素或GSK3酵素，能三倍减低线粒体动物时计的强度。

我们的发现之所以很极为重要主要有两个原因：首先，该分析为硫是如何能用来稳定帕金森氏症病征的情绪反转提供者了一种最初阐释；其次，分析提供者了开发设计最初防帕金森氏症口服最初思路，取而代之口服可能效仿或甚至弱化硫对GSK3的发挥作用，同时并不会造成了因使用硫醋所带给的副发挥作用。

硫醋的副发挥作用仅限于呕吐、痤疮、流汗、手部无力、抽动、镇静等。目前，选择性GSK3的口服已在分析开发设计，因为GSK3已被证明在其他癌症仅限于乳癌和阿尔茨海默氏病中发挥极为重要发挥作用。 Meng医生补充感叹：除了GSK3外，硫醋具在线粒体有广泛的发挥作用肽链。单单堵塞GSK3的口服将能增加硫的“脱靶效应”，兼具契合的优势。

我们的分析仍未确定了选择性GSK3后能较弱性的增进缓冲人体时计脉搏的发挥作用，因此应用该机制开发设计出取而代之一种最初口服来缓冲心率是很有可能的。我们所着手的分析也可能引致造成了疗法帕金森氏症的取而代之方法，但这一点还只能进行具体来感叹的验证。

该分析由医学分析理事会和动物技术和动物科学分析理事会（BBSRC）捐款，并发表在PLoS One上。（动物谷：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.