Dynamic response of microglia/macrophage polarization following demyelination in mice
Dynamic response of microglia/macrophage polarization following demyelination in mice
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DOI：
10.1186/s12974-019-1586-1
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发表时间：
2019-10-17
影响因子：
9.3
通讯作者：
Cai, Jun
中科院分区：
文献类型：
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作者：
Chu, Tianci;Zhang, Yi Ping;Cai, Jun
多发性硬化症（MS）的神经胶质反应，特别是少突胶质细胞祖细胞（OPCs）的募集和分化，预示着MS斑块的髓鞘再生和功能恢复的成功。小胶质细胞/巨噬细胞（M/M）的激活和极化在神经炎症中起着核心作用，调节炎症生态位和脱髓鞘病变中的细胞因子成分，可能影响OPC反应和脱髓鞘和再髓鞘的进展。然而，M/M和OPCs在脱髓鞘和自发髓鞘再生过程中的动态行为尚不清楚，神经炎症在脱髓鞘-髓鞘再生过程中的复杂作用尚不清楚。本研究利用两种具有不同M/M动态模式的局灶性脱髓鞘模型，探讨M/M极化与脱髓鞘-再脱髓鞘过程的相关性。方法观察溶卵磷脂（LPC）和脂多糖（LPS）诱导的两种小鼠局灶性脱髓鞘模型M/M激活/极化和OPC反应的时空特征。分析两种模型在不同阶段的形态学、感觉运动功能、弥散张量成像（DTI）、炎症相关细胞因子和胶质反应的详细区分。结果结果表明，LPC和LPS诱导的损伤在时间和空间上具有明显的差异。与LPC相比，LPS产生弥漫性脱髓鞘病变，脱髓鞘峰值延迟，功能下降。少突胶质细胞、星形胶质细胞和M/M细胞分散在lps诱导的脱髓鞘病变中，但在lpc诱导的病变中呈层状分布。特异性M/M极化与平衡木功能相关的病变模式密切相关。结论本研究阐述了两种局灶性脱髓鞘模型脱髓鞘-再脱髓鞘过程中神经炎症介质和神经胶质反应的时空特征。特异性M/M极化与脱髓鞘-再脱髓鞘过程高度相关，可能通过调节炎症生态位、细胞因子成分和OPC反应。这些发现不仅为理解复杂和动态的胶质细胞表型和行为提供了基础，而且还揭示了在适当的时间促进/抑制某些M/M表型以实现有效的髓鞘再生的潜在靶点。
Background The glial response in multiple sclerosis (MS), especially for recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), predicts the success of remyelination of MS plaques and return of function. As a central player in neuroinflammation, activation and polarization of microglia/macrophages (M/M) that modulate the inflammatory niche and cytokine components in demyelination lesions may impact the OPC response and progression of demyelination and remyelination. However, the dynamic behaviors of M/M and OPCs during demyelination and spontaneous remyelination are poorly understood, and the complex role of neuroinflammation in the demyelination-remyelination process is not well known. In this study, we utilized two focal demyelination models with different dynamic patterns of M/M to investigate the correlation between M/M polarization and the demyelination-remyelination process. Methods The temporal and spatial features of M/M activation/polarization and OPC response in two focal demyelination models induced by lysolecithin (LPC) and lipopolysaccharide (LPS) were examined in mice. Detailed discrimination of morphology, sensorimotor function, diffusion tensor imaging (DTI), inflammation-relevant cytokines, and glial responses between these two models were analyzed at different phases. Results The results show that LPC and LPS induced distinctive temporal and spatial lesion patterns. LPS produced diffuse demyelination lesions, with a delayed peak of demyelination and functional decline compared to LPC. Oligodendrocytes, astrocytes, and M/M were scattered throughout the LPS-induced demyelination lesions but were distributed in a layer-like pattern throughout the LPC-induced lesion. The specific M/M polarization was tightly correlated to the lesion pattern associated with balance beam function. Conclusions This study elaborated on the spatial and temporal features of neuroinflammation mediators and glial response during the demyelination-remyelination processes in two focal demyelination models. Specific M/M polarization is highly correlated to the demyelination-remyelination process probably via modulations of the inflammatory niche, cytokine components, and OPC response. These findings not only provide a basis for understanding the complex and dynamic glial phenotypes and behaviors but also reveal potential targets to promote/inhibit certain M/M phenotypes at the appropriate time for efficient remyelination.