Predictable chronic mild stress promotes recovery from LPS-induced depression
Predictable chronic mild stress promotes recovery from LPS-induced depression
复制标题
可预测的慢性轻度压力可促进 LPS 引起的抑郁症的恢复
DOI：
10.1186/s13041-019-0463-2
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发表时间：
2019-05-03
期刊：
影响因子：
3.6
通讯作者：
Zhao, Ming-gao
中科院分区：
文献类型：
--
作者：
Dang, Ruili;Guo, Yan-yan;Zhao, Ming-gao
临床抑郁症经常与慢性炎症性疾病共病，神经炎症是目前提出的一个关键机制，在重度抑郁症。与不可预测的慢性应激不同，不可预测的慢性应激是一种成熟的抑郁症动物模型，可预测的慢性轻度应激（PCMS）是一种日常生活中经历的常规应激，已被证明可以改善情绪和记忆。在本研究中，我们评估PCMS（每天5分钟的束缚应激4周）对抑郁样行为，神经炎症，氧化应激和pyrin domain containing three（NLRP 3）激活的小鼠进行外周免疫攻击脂多糖（LPS）的影响。我们发现，PCMS促进从LPS诱导的抑郁或焦虑样行为的恢复。与异常行为改变的逆转同时，PCMS抑制LPS诱导的促炎细胞因子表达、小胶质细胞活化和海马中的氧化应激。相应地，PCMS抑制LPS诱导的NLRP 3炎性体组分（NLRP 3、ASC和Caspase-1）的过度活化和白细胞介素1 β（IL-1β）成熟。Nrf 2（核因子（红细胞衍生2）样2）信号传导被证明抑制NLRP 3炎性小体过度活化和氧化应激。在LPS处理的小鼠中，PCMS激活Nrf 2信号传导并抑制硫氧还蛋白（Trx）相互作用蛋白（TXNIP）的表达。总的来说，目前的数据表明，PCMS，相反的严重和不受控制的压力，减轻Nrf 2-TXNIP-Trx系统的损伤，并可能有助于炎症性脑损伤和细胞氧化还原稳态的不平衡，在抑郁症小鼠。这项研究提供了一个机制的联系，PCMS的弹性脂多糖诱导的行为缺陷。
Clinical depression is frequently comorbid with chronic inflammatory disease, and neuroinflammation is currently proposed as a key mechanism in major depressive disorders. Different from unpredictable chronic stress, which is a well-established animal model for depression, predictable chronic mild stress (PCMS), a routine stress experienced in day-to-day life, has been demonstrated to improve mood and memory. In the present study, we assess the effects of PCMS (5 min of daily restrain stress for 4 weeks) on depressive-like behavior, neuroinflammation, oxidative stress, and pyrin domain containing three (NLRP3) activation in hippocampus of mice subjected to peripheral immune challenge by lipopolysaccharide (LPS). We found that PCMS facilitated the recovery from LPS-induced depressive- or anxiety-like behavior. Concurrent with the reversal of abnormal behavioral changes, PCMS suppressed LPS-induced proinflammatory cytokine expression, microglia activation, and oxidative stress in hippocampus. Correspondingly, PCMS inhibited LPS-induced overactivation of NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1), and interleukin 1 beta (IL-1β) maturation. Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling was demonstrated to inhibit NLRP3 inflammasome overactivation and oxidative stress. PCMS activated Nrf2 signaling and inhibited thioredoxin (Trx)-interacting protein (TXNIP) expression in LPS-treated mice. Collectively, present data suggest that PCMS, contrary to severe and uncontrolled stress, alleviated impairments of the Nrf2-TXNIP-Trx system and may contribute to inflammatory brain damage and the imbalance of cellular redox homeostasis in depressed mice. This study provides a mechanistic link to the resilience of PCMS to LPS-induced behavioral deficits.