Unit of Neurology, Department of Systems Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133, Rome, Italy.
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
Mol Neurobiol. 2024 Nov;61(11):8921-8927. doi: 10.1007/s12035-024-04157-w. Epub 2024 Apr 4.
The biological substrate of persistent post-COVID-19 hyposmia is still unclear. However, as many neurodegenerative diseases present with smell impairment at onset, it may theoretically reflect degeneration within the central olfactory circuits. However, no data still exist regarding the post-COVID-19 patients. As the olfactory neurons (ONs) mirror pathological changes in the brain, allowing for tracking the underlying molecular events, here, we performed a broad analysis of ONs from patients with persistent post-COVID-19 OD to identify traces of potential neurodegeneration. ONs were collected through the non-invasive brushing of the olfactory mucosa from ten patients with persistent post-COVID-19 hyposmia (lasting > 6 months after infection) and ten age/sex-matched controls. Immunofluorescence staining for protein quantification and RT-PCR for gene expression levels were combined to measure ONs markers of α-synuclein, amyloid-β, and tau pathology, axonal injury, and mitochondrial network. Patients and controls had similar ONs levels of oligomeric α-synuclein, amyloid-β peptide, tau protein, neurofilament light chain (NfL), cytochrome C oxidase subunit 3 (COX3), and the heat shock protein 60 (HSP60). Our findings thus did not provide evidence for synucleinopathy and amyloid-β mismetabolism or gross traces of neuronal injury and mitochondrial dysfunction within the olfactory system in the early phase of persistent post-COVID-19 hyposmia.
持续性新冠后嗅觉减退的生物学基础仍不清楚。然而,由于许多神经退行性疾病在发病时都伴有嗅觉障碍,因此从理论上讲,这可能反映了中枢嗅觉回路的退化。然而,目前仍没有关于新冠后患者的相关数据。由于嗅觉神经元 (ONs) 反映了大脑的病理变化,可用于追踪潜在的分子事件,因此,我们对持续性新冠后嗅觉减退患者的 ONs 进行了广泛分析,以确定潜在神经退行性变的痕迹。通过对 10 名持续性新冠后嗅觉减退(感染后持续超过 6 个月)患者和 10 名年龄/性别匹配的对照组患者的非侵入性嗅黏膜刷取,收集了 ONs。免疫荧光染色用于蛋白定量,逆转录聚合酶链反应 (RT-PCR) 用于基因表达水平,以测量 ONs 的α-突触核蛋白、淀粉样β 和 tau 病理学、轴突损伤和线粒体网络的标志物。患者和对照组的寡聚α-突触核蛋白、淀粉样β 肽、tau 蛋白、神经丝轻链 (NfL)、细胞色素 C 氧化酶亚基 3 (COX3) 和热休克蛋白 60 (HSP60) 的 ONs 水平相似。因此,我们的研究结果并未在持续性新冠后嗅觉减退的早期阶段提供突触核蛋白病和淀粉样β代谢异常或嗅神经系统内神经元损伤和线粒体功能障碍的大量证据。