Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Division of Neurosurgery, Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Cell Rep. 2023 Dec 26;42(12):113574. doi: 10.1016/j.celrep.2023.113574. Epub 2023 Dec 14.
Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss. While therapies exist to slow MS progression, no treatment currently exists for remyelination. Remyelination, linked to reduced disability in MS, relies on microglia and monocyte-derived macrophages (MDMs). This study aims to understand the role of microglia during remyelination by lineage tracing and depleting them. Microglial lineage tracing reveals that both microglia and MDMs initially accumulate, but microglia later dominate the lesion. Microglia and MDMs engulf equal amounts of inhibitory myelin debris, but after microglial depletion, MDMs compensate by engulfing more myelin debris. Microglial depletion does, however, reduce the recruitment and proliferation of oligodendrocyte progenitor cells (OPCs) and impairs their subsequent differentiation and remyelination. These findings underscore the essential role of microglia during remyelination and offer insights for enhancing this process by understanding microglial regulation of remyelination.
多发性硬化症 (MS) 是一种以髓鞘丢失为特征的炎症性疾病。虽然存在减缓 MS 进展的治疗方法，但目前尚无促进髓鞘再生的治疗方法。髓鞘再生与 MS 残疾程度降低有关，它依赖于小胶质细胞和单核细胞衍生的巨噬细胞（MDM）。本研究旨在通过谱系追踪和耗尽它们来了解小胶质细胞在髓鞘再生中的作用。小胶质细胞谱系追踪表明，小胶质细胞和 MDM 最初都会聚集，但小胶质细胞后来会占据病变部位。小胶质细胞和 MDM 吞噬等量的抑制性髓鞘碎片，但在耗尽小胶质细胞后，MDM 通过吞噬更多的髓鞘碎片来代偿。然而，小胶质细胞耗竭会减少少突胶质细胞前体细胞（OPC）的募集和增殖，并损害它们随后的分化和髓鞘再生。这些发现强调了小胶质细胞在髓鞘再生中的重要作用，并通过了解小胶质细胞对髓鞘再生的调节，为增强这一过程提供了思路。
