Lithium impacts on the amplitude and period of the molecular circadian clockwork.
Lithium impacts on the amplitude and period of the molecular circadian clockwork.
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DOI：
10.1371/journal.pone.0033292
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Meng QJ
中科院分区：
文献类型：
--
作者：
Li J;Lu WQ;Beesley S;Loudon AS;Meng QJ
锂盐已被广泛用于治疗双相情感障碍，这是一种与昼夜节律紊乱相关的精神障碍。锂轻微但持续地延长多种生物行为节律的昼夜周期。为了系统地研究锂对昼夜节律的影响及其潜在机制，我们测量了慢性锂治疗后小鼠体内的运动活动，并在体外追踪了锂处理组织切片/细胞的时钟蛋白动力学（PER2:：荧光素酶）。锂延长运动活动节律周期，延长视交叉上核、肺组织和成纤维细胞的分子振荡周期。此外，我们还发现PER2::LUC在中枢和外周起搏器中的表达和振荡幅度均显著升高。锂离子对PER2::LUC的升高与PER2蛋白稳定性的改变无关，而与PER2基因转录的增加有关。虽然锂和GSK3抑制在时钟周期上表现出相反的作用，但它们以相似的方式上调PER2表达和振荡幅度。总的来说，我们的数据已经确定了锂对中央和外周生物钟中PER2蛋白节律的一种新的振幅增强效应，这可能涉及gsk3介导的信号通路。这些发现可能促进我们对锂在双相情感障碍或其他涉及昼夜节律紊乱的精神疾病中的治疗作用的理解。
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.
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影响因子：
4
作者：
Meng QJ;McMaster A;Beesley S;Lu WQ;Gibbs J;Parks D;Collins J;Farrow S;Donn R;Ray D;Loudon A
通讯作者：
Loudon A
影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U
DOI：
10.1006/bbrc.2000.4169
发表时间：
2001-01-26
影响因子：
3.1
作者：
Ryves, WJ;Harwood, AJ
通讯作者：
Harwood, AJ
DOI：
10.1073/pnas.0811410106
发表时间：
2008-12-30
影响因子：
11.1
作者：
Hirota, Tsuyoshi;Lewis, Warren G.;Kay, Steve A.
通讯作者：
Kay, Steve A.
影响因子：
4.1
作者：
Osland, Teresa M.;Ferno, Johan;Steen, Vidar M.
通讯作者：
Steen, Vidar M.