基础医学与临床 ›› 2019, Vol. 39 ›› Issue (7): 943-948.

• 研究论文 • 上一篇    下一篇

米诺环素增加情绪有关脑区ΔFosB的表达来减轻LPS诱导的小鼠神经炎性反应

李岚岚1,修建波1,沈岩2,许琪3   

  1. 1. 中国医学科学院基础医学研究所 北京协和医学院基础学院
    2. 中国医学科学院基础医学研究所 北京协和医学院 基础学院 医学分子生物学国家重点实验室
    3. 中国医学科学院基础医学研究所
  • 收稿日期:2019-03-11 修回日期:2019-04-18 出版日期:2019-07-05 发布日期:2019-07-02
  • 通讯作者: 许琪 E-mail:qixu@vip.sina.com
  • 基金资助:
    北京市科学技术委员会项目;协和青年基金

Minocycline alleviates LPS-induced neuroinflammation by increasing the expression of ΔFosB in emotion-regulating brain regions in mice

  • Received:2019-03-11 Revised:2019-04-18 Online:2019-07-05 Published:2019-07-02
  • Contact: Qi XU E-mail:qixu@vip.sina.com

摘要: 目的 探究转录因子ΔFosB在米诺环素减轻脂多糖(LPS)诱导的神经炎性反应中的作用。方法 成年C57BL/6小鼠连续3d经腹膜内注射0.9%氯化钠溶液或米诺环素(50 mg/kg),第三天再分别注射0.9%氯化钠溶液或脂多糖(LPS, 0.83mg/kg),注射后6或24 h取样。免疫组化观察特定脑区小胶质细胞形态和ΔFosB的表达,以分析米诺环素对LPS导致神经炎性反应的抑制作用和ΔFosB的表达分布。用Image-Pro Premier 3D分析图像,用GraphPad Prism进行统计学分析。结果 米诺环素可以有效减少蓝斑(LC)中LPS导致的小胶质细胞胞体面积的增加(P < 0.05),减少中枢的炎性反应。同时,米诺环素增加了抑郁症相关脑区LC(P < 0.001),臂旁核(LPB,P < 0.05)和下丘脑室旁核(PVN,P < 0.05)中ΔFosB的表达。 结论 米诺环素可能通过增加情绪有关脑区LC,LPB,PVN中ΔFosB的表达来减轻脂多糖诱导的神经炎性反应。

关键词: 抑郁症, ΔFosB, 米诺环素, 小胶质细胞

Abstract: Objective To investigate the role of ΔFosB as a transcription factor in the reduction of lipopolysaccharide (LPS)-induced neuroinflammation by minocycline. Methods Adult C57BL/6 mice at 10 weeks of age received intraperitoneal (i.p.) injections of saline or minocycline (50 mg/kg) for three consecutive days. On the third day, mice were also injected via i.p. with saline or Escherichia coli LPS (0.83 mg/kg). The morphology of microglia indicating the state of neuroinflammation and ΔFosB as a transcription factor were examined by immunohistochemistry. Images of the staining were analyzed with Image-Pro Premier 3D. Statistical analysis was performed with GraphPad Prism. Results Minocycline alleviated LPS-induced neuroinflammation as evidenced by the reduced activation of microglia in locus coeruleus (LC). Minocycline significantly increased the number of ΔFosB-positive neurons in LC, the lateral parabrachial nucleus (LPB) and paraventricular nucleus of the hypothalamus (PVN). Conclusions Minocycline alleviates LPS-induced neuroinflammation possibly by increasing the expression of ΔFosB in emotion-regulating brain regions including LC, LPB and PVN.

Key words: depression, ΔFosB, minocycline, microglia

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