Behavioral, inflammatory and neurochemical disturbances in LPS and UCMS-induced mouse models of depression
Behavioral, inflammatory and neurochemical disturbances in LPS and UCMS-induced mouse models of depression
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LPS 和 UCMS 诱导的抑郁小鼠模型的行为、炎症和神经化学紊乱
DOI：
10.1016/j.bbr.2017.05.064
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Jianmei Ma
中科院分区：
文献类型：
--
作者：
Xinnan Zhao;Fengrui Cao;Qing Liu;Xinsheng Li;Guoyang Xu;Gang Liu;Yanli Zhang;Xiaohan Yang;Shansong Yi;Fenghua Xu;Kai Fan;Jianmei Ma
各种应激触发的免疫炎症激活在抑郁症的病理生理中起着重要作用。在不同的应激条件下，免疫反应表现出不同的病理特征。然而，关于不同应激性抑郁症的行为、炎症和神经化学变化的比较数据和分析是有限的。为了模拟不同的应激情况，本研究分别给小鼠单次注射LPS（0.5 mg/kg, i.p.）和UCMS（4周）。与ucms应激小鼠相比，lps应激小鼠在FST和TST的静止时间更长，在OFT的外周时间更长。此外，与ucms应激小鼠相比，lps应激小鼠血清和抑郁相关脑区（前额皮质、海马和纹状体）中TNF-α、IL-1β和IL-6的表达和释放明显增强。ELISA结果显示，LPS和UCMS应激后IDO表达显著升高，但LPS应激小鼠前额叶皮层和海马IDO表达增加较多。5-HT和BDNF的减少仅在lps应激小鼠的海马中检测到，但与对照组相比，ucms应激小鼠的所有脑区都检测到。数据表明，LPS诱导的抑郁样行为和免疫激活比UCMS更严重。本研究强烈提示抑郁症患者海马相对更容易受到急性炎症的侵袭，而慢性心理应激更容易引起临床抑郁症的多维症状。我们的研究结果为各种应激性抑郁症的病理生理学提供了更多的见解，也暗示了不同应激模型的潜在适用性。
The immuno-inflammatory activation triggered by various stresses play an important role in pathophysiology of depression. The immune responses display differential pathological characters in different stresses. However, comparative data and analysis on behavioural, inflammatory and neurochemical changes in different stress-induced depression is limited. To imitate different stressful situations, in this study, mice were subjected to a single injection of LPS (0.5 mg/kg, i.p.) and UCMS (4 week period), respectively. LPS-stressed mice showed more immobility time in FST and TST, as well as more time in periphery in OFT than UCMS-stressed mice. Further, LPS-stressed mice showed robuster expression and release of TNF-α, IL-1β and IL-6 in serum and depression-related brain areas (prefrontal cortex, hippocampus and striatum) as compared to UCMS-stressed mice. The ELISA results showed that IDO expression was significantly increased following LPS and UCMS stresses, but more increased IDO expression was observed in prefrontal cortex and hippocampus of LPS-stressed mice. The decrease of 5-HT and BDNF was detected only in hippocampus of LPS-stressed mice, but in overall all the brain areas assessed in UCMS-stressed mice as compared to control. The data indicate that LPS induced more severe depressive-like behaviours and robuster immune activation than UCMS. Our study strongly imply that hippocampus is relatively more vulnerable to acute inflammatory challenge in depression, while chronic psychological stress is more likely to cause the multidimensional symptoms of clinical depression. Our findings provide more insight into pathophysiology in various stress-induced depression and also implicate a potential suitability of different stress models.
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影响因子：
--
作者：
A. Miller;C. Pariante;B. D. Pearce
通讯作者：
A. Miller;C. Pariante;B. D. Pearce
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影响因子：
5.3
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影响因子：
15.1
作者：
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通讯作者：
Schedlowski, Manfred
影响因子：
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作者：
Maes, M;Song, C;Smith, RS
通讯作者：
Smith, RS
影响因子：
10.6
作者：
Dowlati, Yekta;Herrmann, Nathan;Lanctot, Krista L.
通讯作者：
Lanctot, Krista L.