小柯机器人

美国宾夕法尼亚大学医学院Alan L. Landay团队报道病毒感染急性后遗症中的血清素减少。该研究于2023年10月16日发表于国际一流学术期刊《细胞》杂志上。

他们提出了一种机制，将所有四种假设联系在一个单一的途径中，并为治疗干预提供了可行的见解。他们发现COVID-19急性后遗症与血清素减少有关。病毒感染和I型干扰素驱动的炎症通过三种机制减少血清素——肠道对血清素前体色氨酸的吸收减少、血小板过度活化和血小板减少，影响血清素储存。增强MAO介导的血清素周转，外周血清素减少。

反过来，阻碍迷走神经的活动，损害海马的反应和记忆。这些发现为长COVID中与病毒持久性相关的神经认知症状提供了可能的解释，这些症状可能延伸到其他病毒后综合征。

研究人员表示，PASC是一项重大的全球卫生挑战。其病理生理机制尚不清楚，迄今尚未发现有效的治疗方法。目前已有几种假说来解释PASC的病因，包括病毒持续性、慢性炎症、高凝性和自主神经功能障碍。

附：英文原文

Title: Serotonin reduction in post-acute sequelae of viral infection

Author: Andrea C. Wong, Ashwarya S. Devason, Iboro C. Umana, Timothy O. Cox, Lenka Dohnalová, Lev Litichevskiy, Jonathan Perla, Patrick Lundgren, Zienab Etwebi, Luke T. Izzo, Jihee Kim, Monika Tetlak, Hélène C. Descamps, Simone L. Park, Stephen Wisser, Aaron D. McKnight, Ryan D. Pardy, Junwon Kim, Niklas Blank, Shaan Patel, Katharina Thum, Sydney Mason, Jean-Christophe Beltra, Michal F. Michieletto, Shin Foong Ngiow, Brittany M. Miller, Megan J. Liou, Bhoomi Madhu, Oxana Dmitrieva-Posocco, Alex S. Huber, Peter Hewins, Christopher Petucci, Candice P. Chu, Gwen Baraniecki-Zwil, Leila B. Giron, Amy E. Baxter, Allison R. Greenplate, Charlotte Kearns, Kathleen Montone, Leslie A. Litzky, Michael Feldman, Jorge Henao-Mejia, Boris Striepen, Holly Ramage, Kellie A. Jurado, Kathryn E. Wellen, Una O’Doherty, Mohamed Abdel-Mohsen, Alan L. Landay

Issue&Volume: 2023-10-16

Abstract: Post-acute sequelae of COVID-19 (PASC, “Long COVID”) pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.

DOI: 10.1016/j.cell.2023.09.013

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01034-6