微质组织突触和神经元剥离:与神经精神病性狼有关
Yishan Zhou1, Liang Chen2, Xiulan Zheng3
1Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
Journal of cellular and molecular medicine
|March 18, 2024
概括
系统性红斑狼 (SLE) 可以影响大脑,导致神经精神病性狼 (NPSLE). 激活的M1微质细胞有助于神经毒性,但像托法西提尼布这样的药物可以通过减少这种激活来提供治疗效益.
科学领域:
- 神经免疫学 神经免疫学
- 自免疫性疾病 自免疫性疾病
- 神经科学是一个神经科学.
背景情况:
- 系统性红斑狼 (SLE) 是一种复杂的自身免疫性疾病,影响多个器官,包括大脑,导致神经精神病性狼 (NPSLE).
- 微质激活是NPSLE的标志性特征,但微质介导的神经毒性的确切机制仍然不清楚.
- 在SLE患者的脑脊液 (CSF) 中发现了类似M1的高水平的促炎细胞因子,特别是那些有神经精神症状的人.
研究的目的:
- 调查微质激活在神经精神性狼 (NPSLE) 病变发生过程中的作用.
- 在狼小鼠模型中探索抑制微质激活的治疗潜力.
主要方法:
- 从SLE患者的CSF中分析细胞因子水平.
- 在MRL/lpr狼小鼠中进行行为测试 (焦虑,认知).
- 脑组织分析 (微质数,细胞因子表达) 和来自狼小鼠的微质的RNA测序.
- 在体外和体外实验评估微质诱导的神经毒性.
- 在MRL/lpr小鼠中对NPSLE症状和神经病理学对托法西替尼治疗效应的评估.
主要成果:
- MRL/lpr小鼠表现出类似焦虑的行为和认知缺陷,与增加的微质激活和促炎细胞因子相关.
- RNA测序揭示了与狼小鼠的微质细胞中细胞化和M1极化相关的上调基因.
- 激活的微质细胞诱导了体内突触剥离和体内神经元死亡.
- 托法西替尼治疗减少了MRL/lpr小鼠的微质激活,突触/神经元损失和行为异常.
结论:
- 经典激活 (M1) 微质在NPSLE的发病过程中起着重要作用.
- 用米诺环林和托法西提尼布等药物抑制微质激活是NPSLE的一种有希望的治疗策略.
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