Molecular Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, MD E1-07, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
Int J Mol Sci. 2021 May 29;22(11):5818. doi: 10.3390/ijms22115818.
A change in microglia structure, signaling, or function is commonly associated with neurodegeneration. This is evident in the patient population, animal models, and targeted in vitro assays. While there is a clear association, it is not evident that microglia serve as an initiator of neurodegeneration. Rather, the dynamics imply a close interaction between the various cell types and structures in the brain that orchestrate the injury and repair responses. Communication between microglia and neurons contributes to the physiological phenotype of microglia maintaining cells in a surveillance state and allows the cells to respond to events occurring in their environment. Interactions between microglia and astrocytes is not as well characterized, nor are interactions with other members of the neurovascular unit; however, given the influence of systemic factors on neuroinflammation and disease progression, such interactions likely represent significant contributes to any neurodegenerative process. In addition, they offer multiple target sites/processes by which environmental exposures could contribute to neurodegenerative disease. Thus, microglia at least play a role as a significant other with an equal partnership; however, claiming a role as an initiator of neurodegeneration remains somewhat controversial.
小胶质细胞的结构、信号或功能的改变通常与神经退行性变有关。这在患者人群、动物模型和靶向体外检测中都很明显。虽然存在明显的关联，但小胶质细胞是否作为神经退行性变的启动子尚不清楚。相反，动态变化暗示了大脑中各种细胞类型和结构之间的密切相互作用，协调损伤和修复反应。小胶质细胞与神经元之间的通讯有助于维持小胶质细胞处于监视状态的生理表型，并使细胞能够对其环境中发生的事件做出反应。小胶质细胞与星形胶质细胞之间的相互作用尚未得到很好的描述，与神经血管单元的其他成员之间的相互作用也没有得到很好的描述；然而，鉴于系统因素对神经炎症和疾病进展的影响，这种相互作用可能代表了对任何神经退行性过程的重要贡献。此外，它们提供了多个靶点/过程，环境暴露可能通过这些靶点/过程导致神经退行性疾病。因此，小胶质细胞至少作为一个重要的伙伴发挥作用，具有平等的合作关系；然而，声称其作为神经退行性变的启动子的作用仍然存在一些争议。
