研究动态
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中枢先天免疫诱导雄性小鼠对创伤后应激障碍样行为和神经炎症反应的耐受性。

Central innate immunization induces tolerance against post-traumatic stress disorder-like behavior and neuroinflammatory responses in male mice.

发表日期:2024 Aug 26
作者: Minxiu Ye, Haojie Zhu, Xu Lu, Rongrong Yang, Hanxiao Wang, Jie Peng, Hainan Pan, Yunli Fang, Ruiting Shi, Fu Li, Zhuo Chen, Wenfeng Hu, Chao Huang
来源: BRAIN BEHAVIOR AND IMMUNITY

摘要:

创伤后应激障碍(PTSD)是一种与异常升高的神经炎症反应相关的严重精神疾病。抑制神经炎症被认为可以有效改善啮齿类动物的 PTSD 样行为。由于在应激暴露之前预刺激小胶质细胞可以预防神经炎症,因此我们假设预刺激小胶质细胞可以预防动物的创伤后应激障碍。结果表明,在压力暴露前一天,按 50、100 或 500,而不是 10μg/kg,单次注射经典免疫刺激剂脂多糖 (LPS),可以防止修饰诱发的焦虑和恐惧样行为。单次长期应激(mSPS)。时间依赖性分析表明,在应激前一或五天(但不是十天)单次注射 LPS(100μg/kg)可以防止 mSPS 诱发的焦虑和恐惧样行为。第一次注射后 10 天进行第二次低剂量 LPS 注射,或在应激诱导对 mSPS 耐受之前 10 天重复注射 LPS (4 次)。机制研究表明,在应激刺激前一天注射一次 LPS 可以阻止 mSPS 诱导的海马白细胞介素 1β (IL-1β)、肿瘤坏死因子 α (TNF-α) 和 IL-6 mRNA 水平的增加和内侧前额叶皮层。通过米诺环素预处理抑制小胶质细胞或通过 PLX3397 消耗小胶质细胞,消除了低剂量 LPS 预注射对 mSPS 诱导的焦虑和恐惧样行为以及神经炎症反应的预防作用。这些结果表明,小胶质细胞的预刺激可能通过减弱神经炎症反应的发展来防止 PTSD 样行为的发展。这可能有助于制定新策略来防止有害压力对大脑造成的破坏性影响。版权所有 © 2024。由 Elsevier Inc. 出版。
Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder associated with abnormally elevated neuroinflammatory responses. Suppression of neuroinflammation is considered to be effective in ameliorating PTSD-like behaviors in rodents. Since pre-stimulation of microglia prior to stress exposure can prevent neuroinflammation, we hypothesized that pre-stimulation of microglia may prevent PTSD in animals. The results show that a single injection of a classical immune stimulant, lipopolysaccharide (LPS), at 50, 100 or 500, but not 10 μg/kg, one day before stress exposure, prevented the anxiety- and fear-like behaviors induced by modified single prolonged stress (mSPS). The time-dependent analysis shows that a single injection of LPS (100 μg/kg) either one or five, but not ten, days before stress prevented mSPS-induced anxiety- and fear-like behaviors. A second low-dose LPS injection 10 days after the first injection or a repeated LPS injection (4 × ) 10 days before stress induced tolerance to mSPS. Mechanistic studies show that a single injection of LPS one day before stress stimulation prevented mSPS-induced increases in levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 mRNA in the hippocampus and medial prefrontal cortex. Inhibition of microglia by pretreatment with minocycline or depletion of microglia by PLX3397 abolished the preventive effect of low-dose LPS pre-injection on mSPS-induced anxiety- and fear-like behavior and neuroinflammatory responses. These results suggest that pre-stimulation of microglia may prevent the development of PTSD-like behaviors by attenuating the development of neuroinflammatory responses. This could help to develop new strategies to prevent the damaging effects of harmful stress on the brain.Copyright © 2024. Published by Elsevier Inc.