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Sulforaphane triggers a functional elongation of microglial process via the Akt signal

机译：索林素通过AKT信号触发微胶质过程的功能伸长

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摘要

Microglia are a kind of innate immune cells in the nervous system. The amoeboid morphology in microglia indicates a pro-inflammatory status, while their ramified morphologies are associated with anti-neuroinflammation. Recently, we and others have reported that drugs that trigger microglial process elongation may be beneficial for neuroinflammation inhibition. In this study, we found that sulforaphane (SFN), a compound extracted from broccoli sprouts, promotes primary cultured microglial process elongation in both normal and pro-inflammatory conditions in a reversible manner. This pro-elongation effect of SFN was also observed in the prefrontal cortex in vivo and accompanied with an attenuation of pro-inflammatory response as well as an enhancement of anti-inflammatory response in primary cultured microglia. Mechanistic studies revealed that the SFN treatment increased Akt phosphorylation levels in primary cultured microglia and Akt inhibition blocked the effect of SFN on microglial process elongation, suggesting that the regulation of microglial process by SFN is mediated by Akt activation. Functional studies showed that Akt inhibition reversed the effect of SFN on both pro- and anti-inflammatory responses in lipopolysaccharide (LPS)-stimulated microglia. In an inflammation model in vivo, SFN pretreatment not only prevented LPS-induced retractions of microglial process in the prefrontal cortex, but improved LPS-induced behavioral abnormalities in mice, including the increase in immobility time in the tail suspension test and forced swim test as well as the decrease in sucrose preference. These results indicate that the SFN inhibits microglial activation and neuroinflammation-triggered behavioral abnormalities likely through triggering Akt-mediated microglial process elongation. (C) 2019 Elsevier Inc. All rights reserved.
机译：微胶质细胞是神经系统中的一种先天免疫细胞。微胶质细胞的作物形态表明促炎症状态，而其分枝形态与抗神经炎症有关。最近，我们和其他人据报道，引发小胶囊过程伸长的药物可能是有益的神经炎性抑制作用。在这项研究中，我们发现从西兰花芽中提取的亚磺甲烷（SFN），以可逆的方式促进正常和促炎病症中的一次培养的微胶质过程伸长。在体内前额叶皮质中也观察到SFN的这种促进效果，并伴随着促炎反应的衰减以及初级培养的小胶质细胞中的抗炎反应的增强。机械研究表明，SFN治疗增加了初级培养的小凝血细胞和AKT抑制作用的磷酸化水平阻断了SFN对微胶囊过程伸长的影响，表明SFN的微胶质过程调节由AKT活化介导。功能性研究表明，AKT抑制反转了SFN对脂多糖（LPS）刺激性微胶质的促炎和抗炎反应的影响。在体内的炎症模型中，SFN预处理不仅防止了前额叶皮层中的LPS诱导的微胶质过程缩回，而且改善了小鼠中的LPS诱导的行为异常，包括尾悬架试验和强制游泳测试中的不可动脉时间的增加以及蔗糖偏好的减少。这些结果表明，通过触发AKT介导的微胶质过程伸长率，SFN抑制了可能通过触发AKT介导的微胶质过程伸长率的微胶质激活和神经炎症触发的行为异常。 （c）2019 Elsevier Inc.保留所有权利。

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  • 来源
    《The Journal of Nutritional Biochemistry》 |2019年第2019期|共12页
  • 作者

    Wu Yue; Gao Minhui; Wu Jingjing; Hu Peili; Xu Xing; Zhang Yaru; Wang Dan; Chen Zhuo; Huang Chao;

  • 作者单位

    Nantong Univ Sch Pharm Dept Pharmacol 19 Qixiu Rd Nantong 226001 Jiangsu Peoples R China;

    Nantong Univ Sch Pharm Dept Pharmacol 19 Qixiu Rd Nantong 226001 Jiangsu Peoples R China;

    Shanghai Jiao Tong Univ Suzhou Kowloon Hosp Dept Cardiol Sch Med 118 Wansheng St Suzhou 215021 Jiangsu Peoples R China;

    Nantong Univ Sch Pharm Dept Pharmacol 19 Qixiu Rd Nantong 226001 Jiangsu Peoples R China;

    Nantong Univ Sch Pharm Dept Pharmacol 19 Qixiu Rd Nantong 226001 Jiangsu Peoples R China;

    Nantong Univ Sch Pharm Dept Pharmacol 19 Qixiu Rd Nantong 226001 Jiangsu Peoples R China;

    Nantong Univ Sch Pharm Dept Pharmacol 19 Qixiu Rd Nantong 226001 Jiangsu Peoples R China;

    Nantong Univ Invas Technol Dept Nantong Peoples Hosp 1 Affiliated Hosp 2 6 North Rd Haier Xiang Nantong 226001 Jiangsu Peoples R China;

    Nantong Univ Sch Pharm Dept Pharmacol 19 Qixiu Rd Nantong 226001 Jiangsu Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    Sulforaphane; Microglia; Process elongation; Akt; Neuroinflammation;

    机译：亚氟烃;小胶质细胞;过程伸长;akt;神经炎症;

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