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首页> 外文期刊>Journal of neuroinflammation >Interleukin-1 beta converting enzyme is necessary for development of depression-like behavior following intracerebroventricular administration of lipopolysaccharide to mice
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Interleukin-1 beta converting enzyme is necessary for development of depression-like behavior following intracerebroventricular administration of lipopolysaccharide to mice

机译：白介素-1β转换酶对于脑室内给予小鼠脂多糖后的抑郁样行为发展是必需的

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Background Interleukin-1 beta converting enzyme (ICE, caspase 1) is a cysteine protease that processes immature pro-IL-1β into active mature IL-1β. IL-1β is a pro-inflammatory cytokine that mediates many of the physiological and behavioral responses to inflammation. Genetic deletion of ICE has previously been shown to prevent some negative physiologic responses to lipopolysaccharide (LPS)-induced inflammation. Methods Here we used a preclinical murine model to test the hypothesis that ICE is necessary for development of depression-like behaviors following intracerebroventricular (ICV) treatment with LPS. Adult male ICE knockout (ICE KO) and congenic wild-type C57BL/6 J (WT) mice were administered LPS either ICV at 100 ng/mouse or intraperitoneally (IP) at 830 μg/kg body weight or an equal volume of saline as controls. Mice were monitored up to 48 h after treatment for both sickness and depression-like behaviors. Results LPS given ICV induced a loss of body weight in both WT and ICE KO mice. This sickness response was similar between WT and ICE KO mice. As expected, LPS administered ICV increased immobility in the forced swim test (FST) and decreased sucrose preference in WT mice but no change in either of these two depression-like behaviors was observed in ICE KO mice. Expression of TNF-α and CD11b in brain was lower in ICE-KO mice at 24 h following ICV administration of LPS compared to WT mice. In contrast, when LPS was given systemically, sickness response, depression-like behaviors, and expression of these genes were similar between the two strains of mice. Conclusions These findings indicate that ICE plays a specific role in depression-like behavior induced by a central inflammatory stimuli even though it is not required when LPS is administered systemically.
机译：背景技术白介素-1β转换酶（ICE，胱天蛋白酶1）是一种半胱氨酸蛋白酶，可将未成熟的前IL-1β加工成活性的成熟IL-1β。 IL-1β是一种促炎性细胞因子，可介导对炎症的许多生理和行为反应。以前，ICE的基因缺失可以防止对脂多糖（LPS）引起的炎症的某些负面生理反应。方法在这里，我们使用临床前鼠模型来验证ICE对脑室内（ICV）LPS治疗后抑郁样行为的发展是必要的这一假设。对成年雄性ICE基因敲除小鼠（ICE KO）和同基因野生型C57BL / 6 J（WT）小鼠以100 ng /小鼠的ICV或830μg/ kg体重的腹膜内（IP）或等体积的生理盐水给予LPS控件。在治疗后直至48小时，监测小鼠的疾病和抑郁样行为。结果给予ICV的LPS导致WT和ICE KO小鼠体重减轻。 WT和ICE KO小鼠的这种疾病反应相似。如预期的那样，LPS施用的ICV在强制游泳试验（FST）中增加了不动性，并且在WT小鼠中降低了蔗糖偏爱性，但是在ICE KO小鼠中未观察到这两种抑郁症行为中的任何一种改变。与野生型小鼠相比，ICV给药LPS后24小时，ICE-KO小鼠的脑中TNF-α和CD11b表达较低。相反，当系统给予LPS时，两种小鼠之间的疾病反应，抑郁样行为和这些基因的表达相似。结论这些发现表明，ICE在中枢炎性刺激诱发的抑郁样行为中起着特定作用，即使全身给药LPS并不需要它。

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