近日，美国康奈尔大学陈水冰等研究人员合作发现，SARS-CoV-2感染导致多巴胺能神经元衰老。相关论文于2024年1月17日在线发表在《细胞—干细胞》杂志上。

研究人员发现由人类多能干细胞（hPSC）衍生的中脑多巴胺（DA）神经元，对严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）感染具有选择性易感性和纵容性。SARS-CoV-2感染DA神经元会引发炎症和细胞衰老反应。在hPSC衍生的DA神经元中进行的高通量筛选发现了几种FDA批准的药物，它们可以通过预防SARS-CoV-2感染来挽救细胞衰老表型。研究人员还在COVID-19患者的黑质组织中发现了炎症和细胞衰老特征，以及低水平的SARS-CoV-2转录本。

此外，研究人员还在一组严重的COVID-19患者中，观察到神经黑素⁺和酪氨酸羟化酶（TH）⁺DA神经元和纤维数量的减少。这些研究结果表明，hPSC衍生的DA神经元对SARS-CoV-2易感，为COVID-19患者确定了候选神经保护药物，并建议有必要对COVID-19患者的神经问题进行仔细、长期的监测。

据介绍，COVID-19患者通常表现为中枢神经系统和/或周围神经系统功能障碍。

附：英文原文

Title: SARS-CoV-2 infection causes dopaminergic neuron senescence

Author: Liuliu Yang, Tae Wan Kim, Yuling Han, Manoj S. Nair, Oliver Harschnitz, Jiajun Zhu, Pengfei Wang, So Yeon Koo, Lauretta A. Lacko, Vasuretha Chandar, Yaron Bram, Tuo Zhang, Wei Zhang, Feng He, Chendong Pan, Junjie Wu, Yaoxing Huang, Todd Evans, Paul van der Valk, Maarten J. Titulaer, Jochem K.H. Spoor, Robert L. Furler O’Brien, Marianna Bugiani, Wilma D.J. Van de Berg, Robert E. Schwartz, David D. Ho, Lorenz Studer, Shuibing Chen

Issue&Volume: 2024-01-17

Abstract: COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

DOI: 10.1016/j.stem.2023.12.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00442-3