Journal of Inflammation Research (Dec 2021)
Microglia Impede Oligodendrocyte Generation in Aged Brain
Abstract
Weimin Luan,1,2,* Xiqian Qi,3,* Feng Liang,2 Xiaotao Zhang,2 Ziyang Jin,2 Ligen Shi,2 Benyan Luo,1 Xuejiao Dai1 1Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Neurology, Ningbo Municipal Hospital of T.C.M., Ningbo, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuejiao Dai; Benyan LuoDepartment of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 312000, People’s Republic of ChinaTel/Fax +86-571-87235101Email [email protected]; [email protected]: Age-related increase in myelin loss may be responsible for brain atrophy, and the mechanism is not completely understood. We aim to comprehensively delineate oligodendrocyte heterogeneity in young and aged mice and to reveal the underlying mechanism for myelin loss during aging.Methods: Diffusion tensor imaging and immunofluorescent staining were performed to verify the demyelination in the aged brains of both rodents and human. Further, the single-cell RNA sequencing data of all brain cells from young and aged mice were deeply analyzed to identify the subsets of oligodendrocyte lineage cells. Cell-to-cell interaction analysis was performed to detect the mechanism of observed changes in oligodendrocyte generation.Results: Oligodendrocytes were observed to up-regulate several senescence associated genes in aged brain. Four clusters of oligodendrocyte precursor cells (OPCs) were identified in both young and aged brains. The number of those OPCs in basal state was significantly increased, while the OPCs in the procedure of differentiation were immensely decreased in aged brain. Furthermore, it was identified that activated microglia in the aged brain released inflammatory factors to suppress OPC differentiation. Stat1 might be a potential target to transform senescent microglia into tissue repair type to promote oligodendrocyte generation.Conclusion: These results provided a perspective on how age activated microglia could impede remyelination and might give a new therapeutic target for age-related remyelinating diseases.Keywords: remyelination, oligodendrocyte precursor cells, microglia, oligodendrocytes, single cell RNA sequencing
