Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse
Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse
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DOI：
10.1016/j.bbi.2014.07.007
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发表时间：
2015-01-01
影响因子：
15.1
通讯作者：
Coogan, Andrew N.
中科院分区：
文献类型：
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作者：
Anderson, Sean T.;Commins, Sean;Coogan, Andrew N.
败血症后脑病是以认知和情感障碍为特征的败血症幸存者的一种鲜为人知的情况。在这项研究中，我们试图通过对之前存活的脓毒症小鼠进行全面的行为和认知评估来更好地了解这种情况。给小鼠注射脂多糖(5 mg/kg)，一个月后进行一系列测试评估。败血症后的动物在尾部悬挂试验中表现出明显更多的不动，并表现出显著降低的蔗糖偏好。急性氟西汀治疗逆转败血症后动物尾部悬吊试验中不动次数的增加。在新的物体识别任务中，败血症后的动物总体上表现出较少的探索性行为，在高架+迷宫中也表现出更多的焦虑样行为。败血症后的小鼠在Morris水迷宫、8臂放射状迷宫或在新物体识别任务中对新物体的偏好上没有表现出认知障碍的迹象。免疫组织化学分析显示，小胶质细胞标志物CD-11b、F4/80和IBA-1在脓毒症后动物的海马区显著上调，与可塑性相关的即刻早期基因产物ARC和Egr1显著下调。我们还观察到败血症后动物齿状回神经干细胞增殖减少，这是通过BrdU掺入来判断的。与核因子-kappa B途径抑制剂PDTC共同处理可减弱内毒素对大多数受影响参数的长期影响，但不会对神经干细胞的增殖产生影响。这些结果表明，在内毒素诱导的小鼠脓毒症之后，抑郁和焦虑样行为以及神经炎性和神经可塑性相关因子的长期增加，以及PDTC减轻脓毒症的严重程度可以减弱许多这些影响。(C)2014 Elsevier Inc.保留所有权利。
Post-septic encephalopathy is a poorly understood condition in survivors of sepsis that is characterised by cognitive and affective impairments. In this study we have sought to better understand this condition by undertaking a comprehensive behavioural and cognitive assessment of mice who had previously survived sepsis. Mice were treated with lipopolysaccharide (LPS; 5 mg/kg) and one month after this assessed on a battery of tests. Post-septic animals were found to display significantly more immobility in the tail suspension test and show a significantly decreased sucrose preference. Acute fluoxetine treatment reversed the increase in immobility in the tail suspension test in post-septic animals. Post-septic animals also showed less overall exploratory behaviour in the novel object recognition task and also showed increased anxiety-like behaviour in the elevated plus maze. Post-septic mice did not show signs of cognitive impairment, as assessed in the Morris watermaze, the 8-arm radial maze or on preference for the novel object in the novel object recognition task. Immunohistochemical analysis revealed significant upregulation of the microglial marker CD-11b, F4/80 and IBA-1 in the hippocampus of post-septic animals, as well as significant downregulation of the plasticity-related immediate early gene products ARC and EGR1. We also observed a decrease in neural stem cell proliferation in the dentate gyrus of post-septic animals as judged by BrdU incorporation. Co-treatment with the NF-kappa B pathway inhibitor PDTC attenuated the long-lasting effects of LPS on most of the affected parameters, but not on neural stem cell proliferation. These results show that LPS-induced sepsis in the mouse is followed by long-lasting increases in depressive- and anxiety-like behaviours, as well as by changes in neuroinflammatory- and neural plasticity-associated factors, and that attenuation of the severity of sepsis by PDTC attenuates many of these effects. (C) 2014 Elsevier Inc. All rights reserved.