大麻使用和大麻二醇调节TREM2表达的HIV诱导变化:与年龄相关的神经病变发生的影响
Bryant Avalos1, Jacqueline R Kulbe1, Mary K Ford1
1Department of Psychiatry, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Viruses
|October 26, 2024
概括
艾滋病毒感染会影响TREM2的表达,TREM2是神经炎症中的关键蛋白质. 像CBD一样,大麻素可能会逆转这些影响,为艾滋病毒相关的神经认知障碍提供潜在的治疗途径.
科学领域:
- 神经免疫学 神经免疫学
- 神经病毒学 神经病毒学
- 药理学 药理学是指药理学的学科.
背景情况:
- 在骨髓细胞2 (TREM2) 上表达的触发受体在神经炎症和艾滋病毒相关的神经认知障碍 (NCI) 中起作用.
- 艾滋病毒感染者 (PWH) 的大麻使用与减少炎症和神经问题有关.
- 假设TREM2功能障碍是HIV神经病变发生的媒介,并且可以通过大麻素来逆转.
研究的目的:
- 研究TREM2在HIV神经病变发生中的作用.
- 在HIV的背景下,探索大麻和大麻素对TREM2的调节效应.
- 研究艾滋病毒感染个体和动物模型中的TREM2表达和功能.
主要方法:
- 使用EcoHIV感染野生型 (WT) 和TREM2 R47H突变小鼠进行行为和分子分析.
- 使用RNA测序和qPCR检查PWH和没有HIV (PWoH) 的人的单细胞衍生巨细胞 (MDM) 中的TREM2基因表达.
- 通过免疫细胞化学 (ICC) 和ELISA评估TREM2蛋白水平 (膜结合和溶解),并分析行为结果.
主要成果:
- 在WT小鼠中,EcoHIV感染改变了TREM2形式,但不是TREM2 R47H小鼠,在TREM2 R47H小鼠中增加了海马IBA1和记忆缺陷.
- 在PWoH中,TREM2 mRNA水平随着年龄的增长而增加,而不是PWH.
- Cannabidiol (CBD) 治疗增加了 TREM2 mRNA,并且 RNA-seq 显示了大麻使用的 PWH 中与 TREM2 相关的转录的上调调节. 对TREM2的IL1β影响被CBD部分逆转.
结论:
- 艾滋病毒感染显著影响TREM2的表达和功能,导致神经病变发生.
- 大麻使用和CBD显示在调节TREM2表达和减轻与艾滋病毒相关的神经效应方面的潜力.
- 用大麻素向TREM2是一个有希望的治疗策略,用于管理与艾滋病毒相关的神经认知障碍.
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