Severtsev Vsevolod V, Pavkina Margarita A, Ivanets Nikolay N, Vinnikova Maria A, Yakovlev Alexander A
Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, 119048, Russia.
Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical-Biological Agency of the Russian Federation, Moscow, 143007, Russia.
Biochemistry (Mosc). 2024 Nov;89(11):1970-1984. doi: 10.1134/S0006297924110117.
Small extracellular vesicles (sEVs) and their role in mental and addictive disorders are extremely promising research areas. Because of their small size, sEVs can pass through the blood-brain barrier. The membrane of sEVs contain proteins that protect them against destruction by the organism's immune system. Due to these properties, sEVs circulating in the blood can be used as potential biomarkers of processes occurring in the brain. Exposure to psychoactive substances and affects sEV biogenesis and significantly alters the amount of sEVs and chemical composition of their cargo. Based on the published reports, sEVs carry numerous potential biomarkers of addictive pathologies, although the diagnostic significance of these markers still has to be evaluated. A large body of evidence indicates that psychoactive substances influence Rab family GTPases, Toll-like receptors, complement system components, and cytokines. In some studies, the effect of psychoactive substances on sEVs was found to be sex-dependent. It has become commonly accepted that sEVs are involved in the regulation of neuroinflammation and interaction between glial cells and neurons, as well as between peripheral cells and cells of the central nervous system. Here, we formulated a hypothesis on the existence of two mechanisms/stages involved in the effect of psychoactive substances on sEVs: the "fast" mechanism that provides neuroplasticity, and the "slow" one, resulting from the impaired biogenesis of sEVs and formation of aberrant vesicles.
小细胞外囊泡（sEVs）及其在精神和成瘾性疾病中的作用是极具前景的研究领域。由于其体积小，sEVs能够穿过血脑屏障。sEVs的膜含有可保护它们免受机体免疫系统破坏的蛋白质。由于这些特性，血液中循环的sEVs可被用作大脑中发生的过程的潜在生物标志物。接触精神活性物质会影响sEV的生物发生，并显著改变sEVs的数量及其货物的化学成分。根据已发表的报告，sEVs携带许多成瘾性病理的潜在生物标志物，尽管这些标志物的诊断意义仍有待评估。大量证据表明，精神活性物质会影响Rab家族GTP酶、Toll样受体、补体系统成分和细胞因子。在一些研究中，发现精神活性物质对sEVs的影响存在性别依赖性。人们普遍认为，sEVs参与神经炎症的调节以及胶质细胞与神经元之间、外周细胞与中枢神经系统细胞之间的相互作用。在此，我们提出了一个关于精神活性物质对sEVs作用的两种机制/阶段的假说：提供神经可塑性的“快速”机制，以及由sEVs生物发生受损和异常囊泡形成导致的“缓慢”机制。
