Introduction: Major depressive disorder is considered a global public health problem. Inflammatory processes are likely involved in its pathophysiology, but the underlying mechanisms have remained uncertain.Here, we used the model of systemic lipopolysaccharide (LPS) injection to test the hypothesis that depressive-like behaviors occur along with changes in the levels of cytokines and brain-derived neurotrophic factor (BDNF) in the hippocampus (HC), prefrontal cortex (PFC), and hypothalamus (HT), and can be prevented by dexamethasone administration. Methods: Adult C57Bl/6 male mice were first isolated for 10 days, and thereafter received an injection of dexamethasone (6 mg/kg, intraperitoneal [i.p.]), saline followed by LPS (0.83 mg/kg, i.p.), or saline. After 6 h, animals were subjected to the forced-swim test (FST) and open-field tests. Immediately after the behavioral tests, they were euthanized and their brains were collected for the biochemical analyses. Results: LPS increased the immobility time and reduced the distance travelled in the FST and open-field test, respectively. Dexamethasone increased the immobility time in saline-treated mice but reduced this behavior in the LPS group. LPS increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and interferon (IFN)-γ in most of the regions evaluated. Dexamethasone prevented LPS-induced IL-6 in the HC, PFC, and HT. Interestingly, dexamethasone increased IL-4 and IL-10 levels in both the LPS- and saline-treated groups. Although dexamethasone reduced BDNF in saline-treated mice, it prevented LPS-induced reduction in this neurotrophic factor. Conclusion: In summary, dexamethasone decreased proinflammatory and increased anti-inflammatory levels of cytokines and prevented a reduction in BDNF levels induced by the inflammatory stimulus. Thus, the attenuation of depressive-like behavior induced by dexamethasone may be related to the effects on these parameters.
Neuroimmunomodulation

中文翻译：

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抑郁症炎症模型中脑细胞因子和脑源性神经营养因子水平的评估

简介：重度抑郁症被认为是一个全球性的公共卫生问题。其病理生理学可能涉及炎症过程，但其潜在机制仍不确定。在这里，我们使用全身性脂多糖 (LPS) 注射模型来检验以下假设：抑郁样行为随着海马 (HC)、前额叶皮层中细胞因子和脑源性神经营养因子 (BDNF) 水平的变化而发生。 PFC) 和下丘脑 (HT)，并且可以通过施用地塞米松来预防。方法：成年 C57Bl/6 雄性小鼠首先被隔离 10 天，然后接受注射地塞米松（6 毫克/千克，腹膜内 [ip]）、生理盐水，然后是 LPS（0.83 毫克/千克，ip）或生理盐水。6 小时后，对动物进行强迫游泳试验（FST）和露天试验。在行为测试之后，他们立即被实施安乐死，并收集他们的大脑进行生化分析。结果：LPS 分别增加了固定时间并减少了 FST 和露天测试中的行驶距离。地塞米松增加了盐水处理小鼠的不动时间，但减少了 LPS 组的这种行为。在大多数评估区域中，LPS 增加了肿瘤坏死因子 (TNF)-α、白细胞介素 (IL)-6 和干扰素 (IFN)-γ 的水平。地塞米松在 HC、PFC 和 HT 中阻止了 LPS 诱导的 IL-6。有趣的是，地塞米松增加了 LPS 和盐水治疗组的 IL-4 和 IL-10 水平。尽管地塞米松减少了盐水处理小鼠的 BDNF，但它阻止了 LPS 诱导的这种神经营养因子的减少。结论：总之，地塞米松降低了促炎性和增加了细胞因子的抗炎水平，并防止了由炎症刺激引起的 BDNF 水平的降低。因此，地塞米松诱导的抑郁样行为的减弱可能与对这些参数的影响有关。
神经免疫调节