躁郁癥是心境障礙的一組臨床表現(xiàn),，是躁狂發(fā)作和抑郁發(fā)作在同一患者身上發(fā)生的疾病，以躁狂和抑郁交替發(fā)作特點(diǎn)的疾病,。臨床主要表現(xiàn)一組心境或情感顯著而持久的改變,，以情感低落或高漲（可伴或不伴焦慮），伴有相應(yīng)的整體活動(dòng)水平（思維和行為）的改變,，間隙期精神狀態(tài)基本正常，有反復(fù)發(fā)作的傾向,。全球總?cè)丝诘?％至3％受到此種疾病的困擾,。
躁郁癥極端的情緒波動(dòng)與晝夜節(jié)律的中斷有緊密聯(lián)系，晝夜節(jié)律指控制我們身體時(shí)鐘的24小時(shí)節(jié)律,，調(diào)控我們的晝夜活動(dòng),。
在過(guò)去的60多年中，鋰鹽（氯化鋰）一直是治療躁郁癥的中流砥柱,，但早期進(jìn)行一些研究一直試圖找出鋰鹽是否以及如何對(duì)大腦及機(jī)體生物鐘產(chǎn)生影響,。
生命科學(xué)學(xué)院首席研究員Qing-Jun Meng說(shuō)，我們的研究表明鋰有一個(gè)新的,、有效的作用,，即能增加時(shí)鐘節(jié)律的幅度或強(qiáng)度，揭示了鋰與情緒穩(wěn)定,、躁郁癥和生物鐘之間的關(guān)聯(lián)性,。
通過(guò)跟蹤一個(gè)關(guān)鍵時(shí)鐘蛋白的動(dòng)態(tài)變化,，我們發(fā)現(xiàn)鋰通過(guò)阻斷糖原合酶激酶或GSK3酶，能三倍增加細(xì)胞內(nèi)生物時(shí)鐘的強(qiáng)度,。
我們的發(fā)現(xiàn)之所以很重要主要有兩個(gè)原因：首先,，該研究為鋰是如何能用來(lái)穩(wěn)定躁郁癥患者的情緒波動(dòng)提供了一種新的解釋；其次,，研究提供了開(kāi)發(fā)新的抗躁郁癥藥物新的思路,，新藥物可能效仿或甚至增強(qiáng)鋰對(duì)GSK3的作用，同時(shí)并不會(huì)產(chǎn)生因使用鋰鹽所帶來(lái)的副作用,。
鋰鹽的副作用包括惡心,、痤瘡、口渴,、肌肉無(wú)力,、震顫、鎮(zhèn)靜等,。目前,，抑制GSK3的藥物已在研究開(kāi)發(fā)，因?yàn)镚SK3已被證明在其他疾病包括糖尿病和阿爾茨海默氏病中發(fā)揮重要作用,。
Meng醫(yī)生補(bǔ)充說(shuō)：除了GSK3外,，鋰鹽具在細(xì)胞內(nèi)有廣泛的作用位點(diǎn)。單單阻斷GSK3的藥物將能減少鋰的“脫靶效應(yīng)”,，具有獨(dú)特的優(yōu)勢(shì),。
我們的研究已經(jīng)確定了抑制GSK3后能強(qiáng)勁性的促進(jìn)調(diào)節(jié)人體時(shí)鐘節(jié)律的作用，因此應(yīng)用該機(jī)制開(kāi)發(fā)出一種新的藥物來(lái)調(diào)節(jié)生物鐘是很有可能的,。我們所開(kāi)展的研究也可能導(dǎo)致產(chǎn)生治療躁郁癥的新方法,，但這一點(diǎn)還需要進(jìn)行相應(yīng)的測(cè)試。
該研究由醫(yī)學(xué)研究理事會(huì)和生物技術(shù)和生物科學(xué)研究理事會(huì)（BBSRC）資助,，并發(fā)表在PLoS One上,。（生物谷：Bioon）
doi:10.1371/journal.pone.0033292
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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 behavioural 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 have 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.
