Long-lasting effects of sepsis on circadian rhythms in the mouse.
Long-lasting effects of sepsis on circadian rhythms in the mouse.
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DOI：
10.1371/journal.pone.0047087
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Coogan AN
中科院分区：
文献类型：
--
作者：
O'Callaghan EK;Anderson ST;Moynagh PN;Coogan AN
日常活动和生理模式被称为昼夜节律，主要由内源性生物计时系统驱动，主时钟位于视交叉上核。以前的研究已经表明了昼夜节律和免疫系统之间的相互关系，尽管到目前为止，关于免疫挑战对昼夜节律系统的长期调节的探索有限，我们在本研究中正是针对这个问题进行了研究。外周注射脂多糖(5 mg/kg)诱导脓毒症，并监测复苏后的昼夜节律。与对照组相比，败血症后动物昼夜节律性的基本参数(自由奔跑周期和节律幅度，夹带到光/暗周期)没有改变。以前用内毒素处理的动物表现出加速的再捕获，使光/暗周期提前6小时，并且在深夜阶段表现出更大的光刺激诱导的相位提前。5-羟色胺-1a/7激动剂8-OH-DPAT处理后，即刻早期基因c-fos、egr-1和arc的光诱导没有改变，相移也没有改变。败血症后动物视交叉上核时钟基因产物PER2的昼夜节律表达发生改变，在海马区PER1和PER2的表达模式也发生改变。内毒素治疗3个月后，视交叉上核小胶质细胞标志物CD-11b和F4/80持续上调，但各种神经肽、细胞因子和细胞内信号转导分子的表达无明显变化。脓毒症对昼夜节律的影响似乎不是由细胞死亡驱动的，因为在内毒素治疗24小时后，TUNEL和裂解caspase3染色判断视交叉上核内没有细胞凋亡的证据。总体而言，这些数据为感染性休克如何对哺乳动物昼夜节律系统产生慢性影响提供了新的见解。
Daily patterns of activity and physiology are termed circadian rhythms and are driven primarily by an endogenous biological timekeeping system, with the master clock located in the suprachiasmatic nucleus. Previous studies have indicated reciprocal relationships between the circadian and the immune systems, although to date there have been only limited explorations of the long-term modulation of the circadian system by immune challenge, and it is to this question that we addressed ourselves in the current study. Sepsis was induced by peripheral treatment with lipopolysaccharide (5 mg/kg) and circadian rhythms were monitored following recovery. The basic parameters of circadian rhythmicity (free-running period and rhythm amplitude, entrainment to a light/dark cycle) were unaltered in post-septic animals compared to controls. Animals previously treated with LPS showed accelerated re-entrainment to a 6 hour advance of the light/dark cycle, and showed larger phase advances induced by photic stimulation in the late night phase. Photic induction of the immediate early genes c-FOS, EGR-1 and ARC was not altered, and neither was phase-shifting in response to treatment with the 5-HT-1a/7 agonist 8-OH-DPAT. Circadian expression of the clock gene product PER2 was altered in the suprachiasmatic nucleus of post-septic animals, and PER1 and PER2 expression patterns were altered also in the hippocampus. Examination of the suprachiasmatic nucleus 3 months after treatment with LPS showed persistent upregulation of the microglial markers CD-11b and F4/80, but no changes in the expression of various neuropeptides, cytokines, and intracellular signallers. The effects of sepsis on circadian rhythms does not seem to be driven by cell death, as 24 hours after LPS treatment there was no evidence for apoptosis in the suprachiasmatic nucleus as judged by TUNEL and cleaved-caspase 3 staining. Overall these data provide novel insight into how septic shock exerts chronic effects on the mammalian circadian system.
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影响因子：
3.7
作者：
LeSauter J;Lambert CM;Robotham MR;Model Z;Silver R;Weaver DR
通讯作者：
Weaver DR
DOI：
10.4049/jimmunol.1102715
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Logan RW;Zhang C;Murugan S;O'Connell S;Levitt D;Rosenwasser AM;Sarkar DK
通讯作者：
Sarkar DK
影响因子：
2.5
作者：
Horikawa, K;Shibata, S
通讯作者：
Shibata, S
影响因子：
3.5
作者：
Lundkvist GB;Sellix MT;Nygård M;Davis E;Straume M;Kristensson K;Block GD
通讯作者：
Block GD
DOI：
10.4049/jimmunol.1001026
发表时间：
2010-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castanon-Cervantes O;Wu M;Ehlen JC;Paul K;Gamble KL;Johnson RL;Besing RC;Menaker M;Gewirtz AT;Davidson AJ
通讯作者：
Davidson AJ