Microglia, the resident myeloid cells in the central nervous system (CNS) play critical roles in shaping the brain during development, responding to invading pathogens, and clearing tissue debris or aberrant protein aggregations during ageing and neurodegeneration. The original concept that like macrophages, microglia are either damaging (pro-inflammatory) or regenerative (anti-inflammatory) has been updated to a kaleidoscope view of microglia phenotypes reflecting their wide-ranging roles in maintaining homeostasis in the CNS and, their contribution to CNS diseases, as well as aiding repair. The use of new technologies including single cell/nucleus RNA sequencing has led to the identification of many novel microglia states, allowing for a better understanding of their complexity and distinguishing regional variations in the CNS. This has also revealed differences between species and diseases, and between microglia and other myeloid cells in the CNS. However, most of the data on microglia heterogeneity have been generated on cells isolated from the cortex or whole brain, whereas white matter changes and differences between white and grey matter have been relatively understudied. Considering the importance of microglia in regulating white matter health, we provide a brief update on the current knowledge of microglia heterogeneity in the white matter, how microglia are important for the development of the CNS, and how microglial ageing affects CNS white matter homeostasis. We discuss how microglia are intricately linked to the classical white matter diseases such as multiple sclerosis and genetic white matter diseases, and their putative roles in neurodegenerative diseases in which white matter is also affected. Understanding the wide variety of microglial functions in the white matter may provide the basis for microglial targeted therapies for CNS diseases.

小胶质细胞是中枢神经系统 (CNS) 中的常驻骨髓细胞，在发育过程中塑造大脑、应对入侵病原体以及在衰老和神经退行性变期间清除组织碎片或异常蛋白质聚集体方面发挥着关键作用。与巨噬细胞一样，小胶质细胞具有破坏性（促炎性）或再生性（抗炎性）的原始概念已更新为小胶质细胞表型的万花筒视图，反映了它们在维持 CNS 稳态中的广泛作用，以及它们对中枢神经系统疾病，以及帮助修复。包括单细胞/核 RNA 测序在内的新技术的使用导致了许多新的小胶质细胞状态的鉴定，从而可以更好地了解它们的复杂性并区分中枢神经系统的区域变化。这也揭示了物种和疾病之间以及中枢神经系统中小胶质细胞和其他骨髓细胞之间的差异。然而，大多数关于小胶质细胞异质性的数据是在从皮层或全脑分离的细胞上产生的，而白质的变化以及白质和灰质之间的差异却相对缺乏研究。考虑到小胶质细胞在调节白质健康方面的重要性，我们简要介绍了当前关于白质中小胶质细胞异质性的知识、小胶质细胞对 CNS 发育的重要性以及小胶质细胞衰老如何影响 CNS 白质稳态。我们讨论了小胶质细胞如何与多发性硬化症和遗传性白质疾病等经典白质疾病有着错综复杂的联系，以及它们在白质也受到影响的神经退行性疾病中的假定作用。了解白质中小胶质细胞的多种功能可能为中枢神经系统疾病的小胶质细胞靶向治疗提供基础。