Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil.
Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Inflamm Res. 2023 Nov;72(10-11):2073-2088. doi: 10.1007/s00011-023-01798-w. Epub 2023 Oct 14.
The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model.
Wild-type C57BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3).
Mice underwent behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, ELISA, histopathological, immunohistochemical and synaptosome analysis.
Increased viral titers and mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, which is indicative of excitotoxicity, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain. Finally, behavioral analysis showed impaired motor, anhedonia-like and anxiety-like behaviors in animals infected with MHV-3.
In conclusion, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.
本研究旨在通过鼠模型探讨冠状病毒感染后急性后果的神经化学和行为影响。
野生型 C57BL/6 小鼠经鼻腔内（i.n）感染鼠冠状病毒 3（MHV-3）。
对小鼠进行行为测试。感染后第 5 天（5 dpi）进行安乐死，对脑组织进行病毒滴定、ELISA、组织病理学、免疫组织化学和突触体分析。
感染小鼠的大脑皮质观察到病毒滴度增加和轻微的组织学变化，包括神经元变性迹象。重要的是，MHV-3 感染诱导皮质谷氨酸和钙水平升高，表明兴奋性毒性增加，以及脑中促炎细胞因子（IL-6、IFN-γ）水平升高和神经保护介质（BDNF 和 CX3CL1）水平降低。最后，行为分析显示感染 MHV-3 的动物存在运动、快感缺失样和焦虑样行为障碍。
总之，本研究数据模拟了 COVID-19 患者急性神经结局的许多方面。因此，该模型可能为研究冠状病毒感染引起的急性神经后遗症和测试可能的治疗方法提供临床前平台。
