Chronic intermittent cold stress sensitizes neuro-immune reactivity in the rat brain.
Chronic intermittent cold stress sensitizes neuro-immune reactivity in the rat brain.
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DOI：
10.1016/j.psyneuen.2011.02.008
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发表时间：
2011-09
影响因子：
3.7
通讯作者：
Morilak, David A.
中科院分区：
文献类型：
--
作者：
Girotti, Milena;Donegan, Jennifer J.;Morilak, David A.
慢性应激导致许多神经精神疾病，其中HPA轴，认知和神经免疫活性失调。患有重度抑郁症的患者或遭受急性应激的健康个体存在循环促炎标志物水平升高。急性应激还激活啮齿动物外周和大脑中的促炎信号。然而，尽管慢性应激与人类精神病理学有明确的相关性，但长期应激暴露对中枢免疫活性和反应性的影响尚未得到很好的表征。我们的实验室先前已经表明，在大鼠中，慢性间歇性冷应激（CIC应激，4 °C，6小时/天，14天）使HPA对随后的新应激源的反应敏感，并在依赖于前额叶皮质功能的认知灵活性测试中产生缺陷。我们假设CIC应激可能通过改变大脑的神经免疫状态，导致神经元功能障碍，从而发挥其中的一些作用。在这项研究中，我们已经开始解决这个问题，通过确定是否以前暴露于CIC压力可以改变随后的神经免疫反应，急性免疫挑战（脂多糖，LPS）或急性异源性应激（足电击）。我们检测了血浆、下丘脑和前额叶皮质中促炎细胞因子IL 1 β和IL 6、环氧合酶2和趋化因子CXCL 1和MCP-1的反应。CIC胁迫对这些标记物的基础表达没有影响，在胁迫终止后24小时。然而，CIC应激增强了血浆、下丘脑和前额叶皮质中响应于LPS的促炎细胞因子IL 1 β（特别是IL 6）以及趋化因子CXCL 1和MCP-1的急性诱导，并且还使下丘脑IL 1 β对急性足电击的反应敏感。因此，大脑中急性促炎反应的致敏可能介导HPA和认知功能中的一些CIC依赖性变化。
Chronic stress contributes to many neuropsychiatric disorders in which the HPA axis, cognition and neuro-immune activity are dysregulated. Patients with major depression, or healthy individuals subjected to acute stress, present elevated levels of circulating pro-inflammatory markers. Acute stress also activates pro-inflammatory signals in the periphery and in the brain of rodents. However, despite the clear relevance of chronic stress to human psychopathology, the effects of prolonged stress exposure on central immune activity and reactivity have not been well characterized. Our laboratory has previously shown that, in rats, chronic intermittent cold stress (CIC stress, 4 °C, 6h/day, 14 days) sensitizes the HPA response to a subsequent novel stressor, and produces deficits in a test of cognitive flexibility that is dependent upon prefrontal cortical function. We have hypothesized that CIC stress could potentially exert some of these effects by altering the neuro-immune status of the brain, leading to neuronal dysfunction. In this study, we have begun to address this question by determining whether previous exposure to CIC stress could alter the subsequent neuro-immune response to an acute immunological challenge (lipopolysaccharide, LPS) or an acute heterologous stressor (footshock). We examined the response of the pro-inflammatory cytokines, IL1β and IL6, the enzyme cyclooxygenase 2, and the chemokines, CXCL1 and MCP-1 in plasma, hypothalamus and prefrontal cortex. There was no effect of CIC stress on basal expression of these markers 24h after the termination of stress. However, CIC stress enhanced the acute induction of the pro-inflammatory cytokines, IL1β and particularly IL6, and the chemokines, CXCL1 and MCP-1, in plasma, hypothalamus and prefrontal cortex in response to LPS, and also sensitized the hypothalamic IL1β response to acute footshock. Thus, sensitization of acute pro-inflammatory responses in the brain could potentially mediate some of the CIC-dependent changes in HPA and cognitive function.
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影响因子：
3.7
作者：
Dugan LL;Ali SS;Shekhtman G;Roberts AJ;Lucero J;Quick KL;Behrens MM
通讯作者：
Behrens MM
DOI：
10.1038/npp.2010.159
发表时间：
2010-12
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.1
作者：
Johnson, JD;O'Connor, KA;Maier, SF
通讯作者：
Maier, SF
影响因子：
2.5
作者：
Jiang, XH;Guo, SY;Hisamitsu, T
通讯作者：
Hisamitsu, T
影响因子：
4.8
作者：
Ghorbel, MT;Sharman, G;Murphy, D
通讯作者：
Murphy, D