Synergistic and additive actions of a psychosocial stressor and endotoxin challenge: Circulating and brain cytokines, plasma corticosterone and behavioral changes in mice
Synergistic and additive actions of a psychosocial stressor and endotoxin challenge: Circulating and brain cytokines, plasma corticosterone and behavioral changes in mice
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DOI：
10.1016/j.bbi.2007.12.001
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发表时间：
2008-05-01
影响因子：
15.1
通讯作者：
Anisman, Hymie
中科院分区：
文献类型：
--
作者：
Gibb, Julie;Hayley, Shawn;Anisman, Hymie
炎症免疫反应的激活可能会引起神经内分泌和中枢神经化学效应，这让人想起传统应激源引发的效应，当同时给予时，可能会产生协同效应。目前的调查评估了包括社交干扰在内的心理社会应激源是否会增强脂多糖对小鼠的影响。确实观察到，在2-4周的社会隔离(而不是1-7天的治疗)之后重新集结所造成的社会混乱，增强了脂多糖(脂多糖：10微克)刺激疾病行为的效果，以及血浆皮质酮、IL-6、肿瘤坏死因子-α和IL-10水平。对于IL-1β、IL-4或干扰素-γ，类似的作用并不明显。就疾病或血浆皮质酮而言，内毒素和其他应激源(束缚、夹尾巴和巨大噪音)之间的协同作用并不明显，这暂时表明，社会应激源，如重组，可能更强大，或者可能参与有利于协同结果的独特神经或神经内分泌回路。在中枢神经系统内，内毒素和重组应激源协同促进前额叶皮质去甲肾上腺素的利用，并对海马去甲肾上腺素的利用产生相加影响。与对循环细胞因子的影响相反，在经历了重组应激源的动物中，内毒素诱导的海马区、PFC区和孤束核中IL-1β、IL-6和TNF-αmRNA的表达水平降低。鉴于内毒素挑战和社会应激源的联合作用，这些数据被解读为建议基于免疫激活的抑郁模型应该考虑施加免疫挑战的应激源背景。(C)2007 Elsevier Inc.保留所有权利。
Activation of the inflammatory immune response may provoke neuroendocrine and central neurochemical effects that are reminiscent of those elicited by traditional stressors, and when administered concurrently may have synergistic effects. The present investigation assessed whether a psychosocial stressor, comprising social disruption, would augment the effects of lipopolysaccharide in mice. It was indeed observed that the social disruption engendered by a period of 2-4 weeks of social isolation (but not 1-7 days of this treatment) followed by regrouping, enhanced the effects of lipopolysaccharide (LPS: 10 mu g) in the provocation of sickness behavior, as well as plasma corticosterone, IL-6, TNF-alpha and IL-10 levels. Similar effects were not apparent with respect to IL-1 beta, IL-4, or IFN-gamma. Synergy between LPS and other stressors (restraint, tail pinch, and loud noise) was not apparent with respect to sickness or plasma corticosterone, provisionally suggesting that social stressors, such as regrouping, may be more powerful or may engage unique neural or neuroendocrine circuits that favour synergistic outcomes. Within the CNS, the LPS and the regrouping stressor synergistically enhanced NE utilization within the prefrontal cortex, and additively influenced hippocampal NE utilization. In contrast to the effects on circulating cytokines, the LPS-induced elevation of IL-1 beta, IL-6 and TNF-alpha mRNA expression in the hippocampus, PFC and nucleus tractus solitarius was diminished in animals that had experienced the regrouping stressor. In view of the combined actions of LPS challenge and a social stressor, these data are interpreted as suggesting that models of depression based on immune activation ought to consider the stressor backdrop upon which immune challenges are imposed. (c) 2007 Elsevier Inc. All rights reserved.