Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge.
Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge.
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DOI：
10.1186/1742-2094-9-9
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发表时间：
2012-01-16
影响因子：
9.3
通讯作者：
Tansey MG
中科院分区：
文献类型：
--
作者：
Barnum CJ;Pace TW;Hu F;Neigh GN;Tansey MG
有充分的证据表明，心理压力会对许多疾病产生不利影响。最近的证据表明，强烈的压力会增加大脑内的炎症，这是许多疾病的已知介质。然而，引起神经炎症反应的慢性心理应激源的长期结果仍然未知。为了解决这个问题，我们修改了先前描述的大鼠/小鼠捕食应激（PS）模型，以增加相互作用的强度。我们假设这些修饰会增强捕食者-被捕食者的体验，增加被捕食动物的神经炎症和行为功能障碍。此外，另一组小鼠受到慢性不可预测压力（CUS）的修改版本，这是一种经常使用的慢性压力模型，利用包括物理，心理，化学等压力源的组合。CUS模型已被证明通过未知的机制加剧了许多炎症相关疾病。使用这两种模型，我们试图确定：1）慢性PS或CUS是否调节炎症反应作为可能介导行为缺陷的拟议机制，以及2）慢性暴露于纯心理应激源（PS）是否导致与包含心理和物理应激源的CUS模型产生的缺陷相似的缺陷。最后，为了确定急性PS是否具有神经炎症后果，在PS后的不同时间点检查成年小鼠的炎症变化。长期PS的青春期小鼠中脑内炎症的基础表达增加。CUS和慢性PS小鼠对随后的脂多糖攻击也有受损的炎症反应，PS小鼠在慢性应激后表现出增加的焦虑和抑郁样行为。最后，成年小鼠遭受急性掠夺性应激增加了炎症因子的基因表达。我们的研究结果表明，捕食压力，行为学相关的压力源，可以引起神经炎症和行为的变化。掠夺性应激模型可能有助于阐明心理应激调节具有炎症成分的疾病的机制。
There is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown. To address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation. Adolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors. Our results demonstrate that predatory stress, an ethologically relevant stressor, can elicit changes in neuroinflammation and behavior. The predatory stress model may be useful in elucidating mechanisms by which psychological stress modulates diseases with an inflammatory component.
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影响因子：
--
作者：
Danese, Andrea;Moffitt, Terrie E.;Harrington, HonaLee;Milne, Barry J.;Polanczyk, Guilherme;Pariante, Carmine M.;Poulton, Richie;Caspi, Avshalom
通讯作者：
Caspi, Avshalom
早期生活中严峻的家庭气候预示着青春期促炎表型的出现。
影响因子：
8.2
作者：
Miller GE;Chen E
通讯作者：
Chen E
影响因子：
12.4
作者：
Harms, Ashley S.;Barnum, Christopher J.;Tansey, Malu G.
通讯作者：
Tansey, Malu G.
影响因子：
3.2
作者：
Barnum, C. J.;Blandino, P., Jr.;Deak, T.
通讯作者：
Deak, T.
影响因子：
3.3
作者：
Barnum, C. J.;Eskow, K. L.;Dupre, K.;Blandino, P., Jr.;Deak, T.;Bishops, C.
通讯作者：
Bishops, C.