Essential roles of plexin-B3 + oligodendrocyte precursor cells in the pathogenesis of Alzheimer’s disease
Alzheimers & Dementia(2021)
摘要
The role of oligodendrocyte lineage cells, the largest glial population in the adult central nervous system (CNS), in the pathogenesis of Alzheimer’s disease (AD) remains elusive. Here, we developed a culture method for adult oligodendrocyte progenitor cells (aOPCs). Fibroblast growth factor 2 (FGF2) promotes survival and proliferation of NG2 + aOPCs in a serum-free defined medium; a subpopulation (~5%) of plexin-B3 + aOPCs was also found. FGF2 withdrawal decreased NG2 + , but increased plexin-B3 + aOPCs and Aβ1-42 secretion. Plexin-B3 + aOPCs were distributed throughout the adult rat brain, although less densely than NG2 + aOPCs. Spreading depolarization induced delayed cortical plexin-B3 + aOPC gliosis in the ipsilateral remote cortex. Furthermore, extracellular Aβ1-42 accumulation was occasionally found around plexin-B3 + aOPCs near the lesions. In AD brains, virtually all cortical SPs were immunostained for plexin-B3, and plexin-B3 levels increased significantly in the Sarkosyl-soluble fractions. These findings suggest that plexin-B3 + aOPCs may play essential roles in AD pathogenesis, as natural Aβ-secreting cells.
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关键词
Alzheimer’,s disease,adult oligodendrocyte progenitor cells,plexin-B3,amyloid β,: fibroblast growth factor 2,cortical spreading depression
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