COVID-19 中央和外围 kynurenine 途径代谢物:对神经和免疫反应的影响
Xueqi Li1, Arvid Edén2, Susmita Malwade1
1Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden.
Brain, behavior, and immunity
|November 30, 2024
概括
幸存者COVID-19经历长期的认知问题与 kynurenine 途径相关. 这项研究在COVID-19患者的大脑和血液中发现了高氨酸代谢物,这表明了新的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 代谢学 代谢学 代谢学
背景情况:
- COVID-19的长期症状包括认知障碍.
- kynurenine 途径与 COVID-19 相关的认知功能障碍有关.
研究的目的:
- 为了研究COVID-19患者脑脊液 (CSF) 和血中的 kynurenine 途径代谢物.
- 将这些代谢物与免疫学和神经学标记物相关联.
- 在COVID-19患者中探索与kynurenine通路相关的基因表达.
主要方法:
- 超高性能液体染色学-并联质谱学 (UPLC-MS/MS) 用于代谢物分析.
- 来自53名COVID-19患者和12名对照组的CSF和血的分析.
- 对基因表达的单细胞转录组数据分析.
主要成果:
- 在COVID-19患者的CSF中增加了林酸 (QUIN) 和氨酸 (KYNA).
- 脑液中金氨酸,金氨酸/氨酸比率 (rKT),QUIN和神经退行性标志物之间的相关性.
- 血 kynurenine 途径激活的增加与 neopterin 相关.
- 在单细胞中升级的类胺2,3-二氧化酶1 (IDO1) 基因表达.
结论:
- 在急性COVID-19中显著激活了外周 kynurenine 途径.
- 在COVID-19中,首次确定了中枢神经系统中 kynurenine 代谢物升高的情况.
- 周围炎症和IDO1过度表达可能会驱动kynurenine通路的激活.
- 阻止金氨酸运输可以减轻COVID-19的神经毒性影响.
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