Das Aniruddha, Icardi Jacob, Borovicka Julie, Holden Sarah, Harrison Henry F, Hirsch Alec J, Raber Jacob, Dana Hod
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Commun Biol. 2025 Jul 3;8(1):993. doi: 10.1038/s42003-025-08435-8.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes a systemic infection that affects the central nervous system. However, its high infectivity makes comprehensive research with the active virus challenging. Here, we use virus-like particles (VLPs) to explore how exposure to SARS-CoV-2 proteins affects brain activity patterns in wild-type mice and in mice that express the human tau protein. VLP exposure elicits changes in corticosterone and distinct chemokine levels. Longitudinal two-photon microscopy recordings in primary somatosensory and motor cortices reveal substantial short-term increases in cortical activity in VLP-injected mice, with increased stimulus-evoked activity in both genotypes and elevated spontaneous activity in the human tau genotype only. Vehicle-injected human tau mice also show increases in cortical activity patterns. Over the following weeks, activity metrics partially subside but do not completely return to baseline levels. Overall, our data suggest that exposure to SARS-CoV-2 VLPs leads to strong short-term disruption of cortical activity patterns in mice with long-term residual effects. Middle-aged human tau mice, which have a more vulnerable genetic background and overexpression of the tau protein, exhibit more severe pathobiology and may be at risk for more adverse outcomes.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）会引发一种影响中枢神经系统的全身性感染。然而，其高传染性使得对活病毒进行全面研究具有挑战性。在此，我们使用病毒样颗粒（VLP）来探究接触SARS-CoV-2蛋白如何影响野生型小鼠以及表达人类tau蛋白的小鼠的脑活动模式。VLP暴露会引发皮质酮和不同趋化因子水平的变化。对初级体感皮层和运动皮层进行的纵向双光子显微镜记录显示，注射VLP的小鼠皮层活动在短期内大幅增加，两种基因型小鼠的刺激诱发活动均增加，而仅人类tau基因型小鼠的自发活动增加。注射溶剂的人类tau小鼠的皮层活动模式也有所增加。在接下来的几周内，活动指标部分消退，但并未完全恢复到基线水平。总体而言，我们的数据表明，接触SARS-CoV-2 VLP会导致小鼠皮层活动模式在短期内受到强烈干扰，并产生长期残留影响。中年人类tau小鼠具有更易受损的遗传背景且tau蛋白过度表达，表现出更严重的病理生物学特征，可能面临更多不良后果的风险。
