Lithium effects on circadian rhythms in fibroblasts and suprachiasmatic nucleus slices from Cry knockout mice.
Lithium effects on circadian rhythms in fibroblasts and suprachiasmatic nucleus slices from Cry knockout mice.
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DOI：
10.1016/j.neulet.2016.02.030
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发表时间：
2016-04-21
影响因子：
2.5
通讯作者：
Welsh DK
中科院分区：
文献类型：
--
作者：
Noguchi T;Lo K;Diemer T;Welsh DK
锂被广泛用于治疗双相情感障碍，这是一种与昼夜节律紊乱有关的神经精神疾病。已知锂可以延长昼夜节律的周期并增加其振幅。这些作用的一个可能途径涉及抑制糖原合成酶激酶-3 β（GSK-3β），其调节β 2（一种决定昼夜节律周期的典型时钟蛋白）的降解。虽然没有证据表明GSK-3β直接磷酸化β 1，但已知其在调节昼夜节律周期和相位中发挥重要作用。在本文中，我们测试了锂通过昼夜节律影响昼夜节律的假设。我们培养了成纤维细胞和视交叉上核（SCN）切片，大脑的主昼夜节律起搏器，来自Cry 1-/-，Cry 2-/-或野生型（WT）小鼠，携带PER 2 β LUC昼夜节律报告基因。在培养基中应用锂，并测量PER 2表达的昼夜节律。在WT和Cry 2-/-成纤维细胞中，10 mM锂增加PER 2表达和节律振幅，但1 mM锂不影响周期或振幅。在非节律性Cry 1-/-成纤维细胞中，10 mM锂增加PER 2表达。在SCN切片中，1 mM锂在所有基因型中延长了101 h，但除Cry 2-/- SCN外，对振幅无影响。因此，WT成纤维细胞中锂的振幅增强作用不受Cry 2敲除的影响，并且在不存在周期延长的情况下发生，而WT SCN中锂的周期延长作用不受Cry 1或Cry 2敲除的影响，并且在不存在节律放大的情况下发生，这表明锂对昼夜节律的这两种作用独立于昼夜节律并且彼此独立。
Lithium is widely used as a treatment of bipolar disorder, a neuropsychiatric disorder associated with disrupted circadian rhythms. Lithium is known to lengthen period and increase amplitude of circadian rhythms. One possible pathway for these effects involves inhibition of glycogen synthase kinase-3β (GSK-3β), which regulates degradation of CRY2, a canonical clock protein determining circadian period. Although there is no evidence that GSK-3β directly phosphorylates CRY1, it is known to play important roles in regulating circadian period and phase. In this paper, we tested the hypothesis that lithium affects circadian rhythms through CRYs. We cultured fibroblasts and slices of the suprachiasmatic nucleus (SCN), the master circadian pacemaker of the brain, from Cry1-/-, Cry2-/-, or wild-type (WT) mice bearing the PER2∷LUC circadian reporter. Lithium was applied in the culture medium, and circadian rhythms of PER2 expression were measured. In WT and Cry2-/- fibroblasts, 10 mM lithium increased PER2 expression and rhythm amplitude, but 1 mM lithium did not affect either period or amplitude. In non-rhythmic Cry1-/- fibroblasts, 10 mM lithium increased PER2 expression. In SCN slices, 1 mM lithium lengthened period ∼1 h in all genotypes, but did not affect amplitude except in Cry2-/- SCN. Thus, the amplitude-enhancing effect of lithium in WT fibroblasts was unaffected by Cry2 knockout and occurred in the absence of period-lengthening, whereas the period-lengthening effect of lithium in WT SCN was unaffected by Cry1 or Cry2 knockout and occurred in the absence of rhythm amplification, suggesting that these two effects of lithium on circadian rhythms are independent of CRYs and of each other.
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影响因子：
2.8
作者：
Noguchi T;Wang CW;Pan H;Welsh DK
通讯作者：
Welsh DK
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：
64.5
作者：
Ukai-Tadenuma, Maki;Yamada, Rikuhiro G.;Ueda, Hiroki R.
通讯作者：
Ueda, Hiroki R.
DOI：
10.4161/cc.8.24.10273
发表时间：
2009-12-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Spengler ML;Kuropatwinski KK;Schumer M;Antoch MP
通讯作者：
Antoch MP
影响因子：
2.8
作者：
Schnell, Anna;Sandrelli, Federica;Albrecht, Urs
通讯作者：
Albrecht, Urs