Does prior sepsis alter subsequent circadian and sickness behaviour response to lipopolysaccharide treatment in mice?
Does prior sepsis alter subsequent circadian and sickness behaviour response to lipopolysaccharide treatment in mice?
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DOI：
10.1007/s00702-013-1124-8
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发表时间：
2015-08-01
影响因子：
3.3
通讯作者：
Coogan, Andrew N.
中科院分区：
文献类型：
--
作者：
Anderson, Sean T.;O'Callaghan, Emma K.;Coogan, Andrew N.
先前的数据表明，先前的免疫挑战史可能会影响对随后的免疫挑战的中枢和行为反应，要么通过启动机制导致反应夸大，要么通过内毒素耐受导致反应减弱。在这组实验中，我们研究了以前脂多糖(LPS)诱导的脓毒症是如何形成对随后较低剂量的LPS治疗的反应的。在给予内毒素(5 mg/kg)或生理盐水治疗后，允许小鼠恢复3-4个月，然后用较小剂量的内毒素(100微克/公斤)攻击以评估疾病行为。在开场测试和尾部悬挂测试中的表现被评估，没有证据表明先前的脓毒症改变了内毒素治疗后的疾病或抑郁样行为。然后，我们检查了小鼠的昼夜节律系统对脂多糖的反应。我们发现，在对照组动物中，内毒素诱导了行为节律的显著延迟，而败血症后动物(脓毒症后4-6周)则不是这样，这表明先前的脓毒症改变了昼夜节律系统对随后免疫挑战的反应性。我们进一步评估了内毒素对对照组或败血症后动物海马区和视交叉上核(SCN；主要昼夜节律起搏器)即刻早期基因c-Fos和Egr1的诱导作用，发现败血症后动物在海马区表达升高，但在SCN没有表达。这些数据表明，先前的脓毒症对小鼠随后的免疫挑战的行为和分子反应有一定影响。
Previous data has shown that prior history of immune challenge may affect central and behavioural responses to subsequent immune challenge, either leading to exaggerated responses via priming mechanisms or lessened responses via endotoxin tolerance. In this set of experiments we have examined how previously lipopolysaccharide (LPS)-induced sepsis shapes the response to subsequent treatment with lower dose LPS. After treatment with LPS (5 mg/kg) or saline mice were allowed to recover for 3-4 months before being challenged with a lower dose of LPS (100 mu g/kg) for assessment of sickness behaviours. Performance on the open field test and the tail suspension test was assessed, and no evidence was found that prior sepsis altered sickness or depressive-like behaviour following LPS treatment. We then examined the responsiveness of the circadian system of mice to LPS. We found that in control animals, LPS induced a significant phase delay of the behavioural rhythm and that this was not the case in post-septic animals (4-6 weeks after sepsis), indicating that prior sepsis alters the responsivity of the circadian system to subsequent immune challenge. We further assessed the induction of the immediate early genes c-Fos and EGR1 in the hippocampus and the suprachiasmatic nucleus (SCN; the master circadian pacemaker) by LPS in control or post-septic animals, and found that post-septic animals show elevated expression in the hippocampus but not the SCN. These data suggest that previous sepsis has some effect on behavioural and molecular responses to subsequent immune challenge in mice.