神经损伤与功能重建2026，Vol.21Issue(1)：后插1-后插1,1.DOI:10.16780/j.cnki.sjssgncj.202601014
清除小胶质细胞可促进再髓鞘化过程中皮质少突胶质细胞密度的增加
Depletion of Microglia Increases Cortical Oligodendrocyte Density During Remyelination
Hannah Katherine Loo 1Joseph Gallegos 1Christine Mialki 1Gregory E Perrin 1Thomas Malloy 1Jennifer L Orthmann-Murphy 1王晶1
作者信息
摘要
Abstract
Cortical demyelination is a critical contributor to progressive disease in multiple sclerosis(MS).The barriers to cortical remye-lination following demyelination are not fully understood,and there are no remyelinating treatments for MS.We previously took advan-tage of the spatial and temporal resolution of longitudinal in vivo imaging to study cortical oligodendrocyte regeneration following cupri-zone-induced demyelination and found that oligodendrocyte regeneration was impaired.In this study,we investigated whether cortical re-active microglia disrupt oligodendrocyte regeneration.To do so,we used a combination of in situ RNA and immunofluorescence labeling to characterize cortical microglia reactive states following cuprizone-mediated demyelination.We then depleted cortical microglia by ad-ministering a Csf1r inhibitor during the recovery period from cuprizone and quantified oligodendrocyte recovery.We found that following cortical demyelination,deep cortical microglia change morphology,downregulate homeostatic markers(P2RY12,TMEM119),and upregu-late a marker(CD68)associated with activated macrophages.These reactive changes persisted through early recovery post-cuprizone but resolved by late recovery.Depleting cortical microglia post-cuprizone restored the baseline density of deep cortical ASPA+oligodendro-cytes at early and late recovery.There were also more deep cortical BCAS1+differentiating oligodendrocytes at early recovery when mi-croglia were depleted,suggesting that transient deep cortical reactive microglia impair oligodendrocyte differentiation following demyelin-ating injury.Together,we found that cortical microglia adopt spatially restricted reactive functions after demyelination and deep cortical re-active microglia transiently reduce differentiating oligodendrocytes.A potential therapeutic strategy for progressive MS could involve tar-geting transiently reactive microglia at the right time and place in cortical lesions to promote oligodendrocyte regeneration.关键词
皮质/氯化铜/小胶质细胞/少突胶质细胞/再髓鞘化Key words
cortex/cuprizone/microglia/oligodendrocytes/remyelination分类
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Hannah Katherine Loo,Joseph Gallegos,Christine Mialki,Gregory E Perrin,Thomas Malloy,Jennifer L Orthmann-Murphy,王晶..清除小胶质细胞可促进再髓鞘化过程中皮质少突胶质细胞密度的增加[J].神经损伤与功能重建,2026,21(1):后插1-后插1,1.
