小柯机器人

英国爱丁堡大学Veronique E. Miron研究团队发现，小胶质细胞调节中枢神经系统髓鞘的生长和完整性。2022年12月14日，《自然》杂志在线发表了这项成果。

研究人员表明，常驻的小胶质细胞对维持小鼠和人类成年后的髓鞘健康至关重要。结果证明，小胶质细胞对发育期的髓鞘形成是不需要的。然而，它们对于随后的髓鞘生长和相关的认知功能的调节，以及通过防止髓鞘变性来保持髓鞘的完整性是必需的。研究人员表明，由于小胶质细胞的缺失而导致的髓鞘健康丧失，与脂质代谢改变的髓鞘化少突胶质细胞状态的出现有关。此外，这一机制是通过破坏TGFβ1-TGFβR1轴来调节的。这些研究结果提示，在髓鞘生长和完整性失调的情况下，如衰老和神经退行性疾病，小胶质细胞可作为治疗靶标。

据介绍，中枢神经系统中的神经元轴突的功能需要髓鞘，但支持髓鞘健康的机制尚不清楚。虽然中枢神经系统中的巨噬细胞与髓鞘健康有关，但哪些巨噬细胞群参与其中以及它们影响哪些方面，目前还不清楚。

附：英文原文

Title: Microglia regulate central nervous system myelin growth and integrity

Author: McNamara, Niamh B., Munro, David A. D., Bestard-Cuche, Nadine, Uyeda, Akiko, Bogie, Jeroen F. J., Hoffmann, Alana, Holloway, Rebecca K., Molina-Gonzalez, Irene, Askew, Katharine E., Mitchell, Stephen, Mungall, William, Dodds, Michael, Dittmayer, Carsten, Moss, Jonathan, Rose, Jamie, Szymkowiak, Stefan, Amann, Lukas, McColl, Barry W., Prinz, Marco, Spires-Jones, Tara L., Stenzel, Werner, Horsburgh, Karen, Hendriks, Jerome J. A., Pridans, Clare, Muramatsu, Rieko, Williams, Anna, Priller, Josef, Miron, Veronique E.

Issue&Volume: 2022-12-14

Abstract: Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health1, it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1–TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease2,3.

DOI: 10.1038/s41586-022-05534-y

Source: https://www.nature.com/articles/s41586-022-05534-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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