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通过CRYAB/STAT4-SHH轴,WIF-1有助于狼引起的神经心理缺陷

Liping Tan^1,2, Yu Fan^1,2, Xinyi Xu³

¹The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.

Arthritis research & therapy

|October 24, 2024

概括

Wnt抑制因子-1 (WIF-1) 通过激活微质细胞和破坏血脑屏障 (BBB) 来恶化狼认知障碍. 抑制WIF-1或使用对称二甲基氨酸 (SDMA) 显示神经精神性狼的治疗潜力.

科学领域:

神经科学是一个神经科学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

神经精神系统性红斑狼 (NPSLE) 与认知能力下降,微质激活和血脑屏障 (BBB) 破坏有关.
在NPSLE脑脊液中发现了Wnt抑制因子-1 (WIF-1),但其在认知障碍中的作用尚不清楚.

研究的目的:

研究Wnt抑制因子-1 (WIF-1) 在狼引起的认知功能障碍中的作用.
探索针对WIF-1或在NPSLE小鼠模型中使用对称二甲基氨酸 (SDMA) 的治疗潜力.

主要方法:

使用的MRL/lpr是易患狼和因伊米奎莫德诱导的狼的小鼠模型.
在脑内进行内注射的重组WIF-1 (rWIF-1) 或编码sh-WIF-1 (AAV-shWIF-1) 的腺相关病毒.
进行行为测试,组织病理学,流细胞计和分子分析.

主要成果:

在狼小鼠中,rWIF-1注射加剧了认知缺陷,BBB泄漏和微质激活.
AAV-shWIF-1治疗导致NPSLE症状显著缓解.
通过CRYAB/STAT4-SHH通路,WIF-1诱导了微质的促炎反应和BBB透性.
SDMA缓解了WIF-1引起的损害,并恢复了SHH水平.

结论:

WIF-1通过CRYAB/STAT4-SHH轴促进微质激活和BBB破坏,从而加剧狼引起的认知功能障碍.
通过减轻WIF-1的影响,SDMA证明了治疗NPSLE的治疗潜力.

关键词:

血液-大脑屏障是什么?微质细胞中的微质细胞神经精神病系统性红血性狼.在WIF-1中使用WIF-1.

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