Impact of THC on Extracellular Vesicle Signaling

鉴于最近美国大麻使用量的增加，迫切需要更清楚地了解 大麻素对中枢和外周信号机制的影响。中的主要精神活性成分 大麻，Δ9-四氢大麻酚(THC)，已被证明直接作用于大麻素受体。这些 受体在中枢和外周细胞群中都有表达，已被证明可以分泌 细胞外小泡，包括脉络丛、神经元、胶质细胞和脂肪细胞。这次会议的主要目标是 建议研究THC对脑和血液中细胞外小泡信号的影响以及 确定一组与THC使用相关的生物标志物。为了进一步验证生物标记物轮廓的选择性，RNA 在另一种通常与大麻共同使用的药物尼古丁存在的情况下，研究人员将比较其表达模式。 此后，我们将确定THC对细胞外小泡密度和RNA载量的影响是否 归因于腹侧被盖区多巴胺能细胞的释放，大脑中的一个区域被证明介导了 加强和奖励滥用药物的特性。通过系统地检测细胞外的变化 囊泡信号与THC暴露和药物联合使用条件有关，这些研究试图揭示 对中枢和外周细胞外信号动力学的重要见解。此外，鉴于该外围设备 MiRNAs已被认为是疾病状态的生物标志物，含有THC的大麻素经常被使用 由患者，如癌症患者，研究结果可能进一步告知其他建议的相关性 临床应用的生物标记物概况。最后，在这个基础上，与大麻素相关的细胞外 信号因子也可能导致识别药物依赖的细胞外机制。 从而为治疗依赖的治疗开发提供潜在的新靶点。

Given the recent increase in cannabis use in the US, there is an urgent need to more clearly understand the effects of cannabinoids on central and peripheral signaling mechanisms. The main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), has been shown to act directly on the cannabinoid receptors. These receptors are expressed in both central and peripheral cellular populations that have been shown to secrete extracellular vesicles, including the choroid plexus, neurons, glia, and adipocytes. The main goals of this proposal are to investigate the effects of THC on extracellular vesicle signaling in the brain and blood and to identify a panel of biomarkers related to THC use. To further validate the selectivity of the biomarker profile, RNA expression patterns will be compared in the presence of another drug commonly co-used with cannabis, nicotine. Thereafter, we will determine whether THC's effects on extracellular vesicle density and RNA cargo can be attributed to release from dopaminergic cells in the ventral tegmental area, a brain region shown to mediate the reinforcing and rewarding properties of drugs of abuse. By systematically examining changes in extracellular vesicle signaling with THC exposure and relating to drug co-use conditions, these studies seek to reveal important insights into central and peripheral extracellular signaling dynamics. Further, given that peripheral miRNAs have been proposed as biomarkers of disease state, and THC-containing cannabinoids are often used by patients, such as individuals with cancer, findings may further inform on the relevance of other proposed biomarker profiles for clinical applications. Finally, with this foundation, cannabinoid-associated extracellular signaling factors may also lead to the identification of extracellular mechanisms underlying drug dependence and thus potential novel targets for therapeutic development to treat dependence.