Innate immune stimulation prevents the development of anxiety-like behaviors in chronically stressed mice
Innate immune stimulation prevents the development of anxiety-like behaviors in chronically stressed mice
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DOI：
10.1016/j.neuropharm.2022.108950
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发表时间：
2022-01
影响因子：
4.7
通讯作者：
Ruiting Shi;Huijun Liu;Pingping Tan;Zhichao Hu;Yaoying Ma;Minxiu Ye;Yue Gu;Yue Wang;Ting Ye;Yiming Gu;Xu Lu;Chao Huang
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作者：
Ruiting Shi;Huijun Liu;Pingping Tan;Zhichao Hu;Yaoying Ma;Minxiu Ye;Yue Gu;Yue Wang;Ting Ye;Yiming Gu;Xu Lu;Chao Huang
焦虑症是一种常见的心理疾病，它会给社会带来严重的负担。寻找预防焦虑发作的方法对于改善这类疾病引起的社会和个人问题具有重要意义。在本研究中，我们研究了先天免疫预刺激如何影响慢性应激小鼠的焦虑样行为。我们的研究结果表明，在应激暴露前1天单次注射50、100和500 μg/kg剂量的先天免疫刺激剂脂多糖（LPS）可预防慢性社会失败应激（CSDS）诱导的小鼠焦虑样行为。应激前5d单次注射LPS（100 μg/kg）对CSDS诱导的焦虑样行为也有类似的预防作用，而间隔10 d注射LPS与应激后10 d注射LPS对CSDS诱导的焦虑样行为无类似的预防作用。在第一次LPS注射后10天进行第二次LPS注射或在应激暴露前10天进行4 × LPS注射也可以防止CSD诱导的焦虑样行为。此外，在应激暴露前1天单次注射LPS（100 μg/kg）可阻止CSDS小鼠海马和前额皮质中促炎细胞因子的产生。通过米诺环素预处理抑制先天免疫刺激，同时消除了LPS预注射（100 μg/kg）对CSD诱导的焦虑样行为和脑中促炎细胞因子产生的预防作用。我们的研究结果表明，先天免疫系统的预刺激可以防止焦虑样行为的发展和慢性应激小鼠大脑中神经炎症反应的进展。本文是“压力，成瘾和可塑性”特刊的一部分。
Anxiety is a common psychological disease which can induce severe social burdens. Searching methods that prevent the onset of anxiety is of great significance for ameliorating the social and individual problems induced by this type of disease. In this study, we investigated how innate immune pre-stimulation influences the anxiety-like behaviors in chronically stressed mice. Our results showed that a single injection of an innate immune stimulant lipopolysaccharide (LPS) at the dose of 50, 100, and 500 μg/kg 1 day before stress exposure prevented chronic social defeat stress (CSDS)-induced anxiety-like behaviors in mice. A single injection of LPS (100 μg/kg) 5 days before stress exposure produced similar preventive effects on CSDS-induced anxiety-like behaviors, while similar effects were not observed at the condition of 10-days interval between LPS injection and stress exposure. A second LPS injection 10 days after the first LPS injection or a 4 × LPS injection 10 days before stress exposure also prevented CSDS-induced anxiety-like behaviors. Moreover, a single injection of LPS (100 μg/kg) 1 day before stress exposure prevented the production of pro-inflammatory cytokines in the hippocampus and prefrontal cortex of CSDS mice. Suppression of innate immune stimulation by minocycline pretreatment simultaneously abrogated the preventive effect of LPS pre-injection (100 μg/kg) on CSDS-induced anxiety-like behaviors and pro-inflammatory cytokine production in the brain. Our results demonstrated that the pre-stimulation of the innate immune system can prevent the development of anxiety-like behaviors and the progression of the neuroinflammatory responses in the brain in chronically stressed mice.This article is part of the special Issue on ‘Stress, Addiction and Plasticity'.