Program of Neuroscience, Department of Neurobiology, Institute of Biology, Federal Fluminense University, Niterói 24210-201, Rio de Janeiro, Brazil.
National Institute of Science and Technology on Neuroimmunomodulation-INCT-NIM, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21041-250, Rio de Janeiro, Brazil.
Int J Mol Sci. 2024 Mar 29;25(7):3819. doi: 10.3390/ijms25073819.
Microglial cells, the immune cells of the central nervous system, are key elements regulating brain development and brain health. These cells are fully responsive to stressors, microenvironmental alterations and are actively involved in the construction of neural circuits in children and the ability to undergo full experience-dependent plasticity in adults. Since neuroinflammation is a known key element in the pathogenesis of COVID-19, one might expect the dysregulation of microglial function to severely impact both functional and structural plasticity, leading to the cognitive sequelae that appear in the pathogenesis of Long COVID. Therefore, understanding this complex scenario is mandatory for establishing the possible molecular mechanisms related to these symptoms. In the present review, we will discuss Long COVID and its association with reduced levels of BDNF, altered crosstalk between circulating immune cells and microglia, increased levels of inflammasomes, cytokines and chemokines, as well as the alterations in signaling pathways that impact neural synaptic remodeling and plasticity, such as fractalkines, the complement system, the expression of SIRPα and CD47 molecules and altered matrix remodeling. Together, these complex mechanisms may help us understand consequences of Long COVID for brain development and its association with altered brain plasticity, impacting learning disabilities, neurodevelopmental disorders, as well as cognitive decline in adults.
小胶质细胞是中枢神经系统的免疫细胞，是调节大脑发育和大脑健康的关键因素。这些细胞对压力源、微环境变化完全敏感，并积极参与儿童神经回路的构建和成人经历依赖性完全可塑性的能力。由于神经炎症是 COVID-19 发病机制中的已知关键因素，人们可能会预期小胶质细胞功能的失调会严重影响功能和结构的可塑性，导致长新冠发病机制中出现的认知后遗症。因此，了解这种复杂的情况对于确定与这些症状相关的可能分子机制是必要的。在本综述中，我们将讨论长新冠及其与 BDNF 水平降低、循环免疫细胞与小胶质细胞之间的相互作用改变、炎症小体、细胞因子和趋化因子水平升高以及影响神经突触重塑和可塑性的信号通路改变之间的关联，例如 fractalkines、补体系统、SIRPα 和 CD47 分子的表达以及基质重塑的改变。这些复杂的机制可能有助于我们了解长新冠对大脑发育的影响及其与改变的大脑可塑性的关联，从而影响学习障碍、神经发育障碍以及成年人的认知能力下降。
