Lipopolysaccharide repeated challenge followed by chronic mild stress protocol introduces a combined model of depression in rats: Reversibility by imipramine and pentoxifylline
Lipopolysaccharide repeated challenge followed by chronic mild stress protocol introduces a combined model of depression in rats: Reversibility by imipramine and pentoxifylline
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DOI：
10.1016/j.pbb.2014.09.014
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发表时间：
2014-11-01
影响因子：
3.6
通讯作者：
Abdel-Tawab, Ahmed M.
中科院分区：
文献类型：
--
作者：
Elgarf, Al-Shaimaa A.;Aboul-Fotouh, Sawsan;Abdel-Tawab, Ahmed M.
目的：本研究探讨了低剂量脂多糖（LPS）和慢性轻度应激（CMS）联合重复刺激的影响。这种组合暴露被认为使动物暴露于更现实的挑战，可在不同水平上进行测试（行为，神经化学，免疫组织化学和基因表达）。神经胶质细胞的作用也进行了检查。另外，研究了三环类抗抑郁药丙咪嗪和抗TNF-α pentoxyphylline的慢性给药的效果。在2周内，CMS方案持续4周或LPS持续2周，然后CMS持续4周。将两组大鼠暴露于LPS/CMS方案，并用丙咪嗪或戊己茶碱治疗。大鼠进行了检查的行为，神经化学和基因表达的changes.Results：动物暴露于LPS/CMS阐述抑郁样症状，血清皮质酮和TNF-α水平显着增加相比，在盐水，LPS或CMS组。与盐水、LPS或CMS组相比，LPS/CMS模型中海马犬尿氨酸/色氨酸比率和TNF-α基因表达显著增加。免疫组化结果仔细检查了检查效果的地形图。丙咪嗪或喷替福林慢性治疗显着改善的行为，神经化学，免疫组化和TNF-α基因表达的变化诱导的LPS/CMS protocol.Conclusion：这项研究提供了线索的神经生物学过程的基础上，至少，抑郁症的亚型。它强调了应激和免疫炎症通路在抑郁症发病机制中可能的相互作用，并提出了一种新的抑郁症动物模型，解决了这些通路。(C)2014爱思唯尔公司All rights reserved.
Objectives: The present study examined the effect of combined exposure to repeated challenge using low doses of lipopolysaccharide (LPS) and chronic mild stress (CMS) together. This combined exposure is thought to expose the animals to more realistic challenges, testable on different levels (behavioral, neurochemical, immunohistochemical and gene expression). The role of glial cells was examined, as well. Additionally, the effects of chronic administration of the tricyclic antidepressant imipramine and the anti-TNF-alpha pentoxyphylline were investigated.Methods: Wistar rats were exposed to either repeated LPS (50 mu g/kg i.p.) over 2 weeks, CMS protocol for 4 weeks or LPS over 2 weeks then 4 weeks of CMS. Two groups of rats were exposed to LPS/CMS protocol and treated with either imipramine or pentoxifylline. Rats were examined for behavioral, neurochemical and gene expression changes.Results: Animals exposed to LPS/CMS elaborated depressive-like symptoms with significant increase in both serum corticosterone and TNF-alpha levels compared to those in the saline, LPS or CMS groups. Hippocampal kynurenine/tryptophan ratio and TNF-alpha gene expression showed significant increase in the LPS/CMS model compared to those in saline, LPS or CMS groups. The immunohistochemical findings scrutinized the topography of the examined effects. Chronic treatment with imipramine or pentoxifylline significantly ameliorated the behavioral, neurochemical, immunohistochemical and TNF-alpha gene expression changes induced by the LPS/CMS protocol.Conclusion: This study gave a clue to the neurobiological processes underlying, at least, the subtypes of depressive disorders. It highlighted the possible interactions between stress and immune-inflammatory pathways in the pathogenesis of depression and suggested a new animal model of depression that addresses these pathways. (C) 2014 Elsevier Inc. All rights reserved.