Mar 31, 2020

Essential roles of plexin-B3+ oligodendrocyte precursor cells in the pathogenesis of Alzheimer's disease

BioRxiv : the Preprint Server for Biology
N. Nihonmatsu-Kikuchi

Abstract

The roles played by oligodendrocyte (OL) lineage cells, the largest glial population in the adult CNS, in the pathogenesis of Alzheimer's disease (AD) remain elusive. Here, we show a newly developed culture method for adult OL progenitor cells (aOPCs) and identify novel plexin-B3-expressing (plexin-B3+) aOPCs as potential amyloid {beta} peptides (A{beta})-secreting cells. Fibroblast growth factor 2 (FGF2) promotes the survival and proliferation of aOPCs in a serum-free defined medium. Although the whole expression profiles of the expanded aOPCs closely resemble those of in vivo OPCs, we found a subpopulation (up to 5%) of plexin-B3+/olig2+ aOPCs in the cultures growing in FGF2. FGF2 withdrawal decreased NG2+, but increased plexin-B3+ aOPCs with increased APP expression, A{beta}1-40, -42 secretions and A{beta}1-42/total A{beta} ratios in association with cored senile plaque-like morphological changes. In vivo, plexin-B3+ aOPCs are distributed throughout the adult brain, although less densely so than NG2+ aOPCs. Spreading depolarization, a type of brain injury, induced unique delayed cortical plexin-B3+ aOPC gliosis in the ipsilateral, but not in the contralateral, remote cortex. In AD brains, virtually all senile plaques in the ...Continue Reading

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Mentioned in this Paper

SOCS1 gene
Peptide Synthesis Technique
Cis, cis, cis, cis-(5.5.5.4)-1-azafenestrane
Cleaved
SOCS1 wt Allele
Amino Acids, I.V. solution additive
Nucleic Acid Sequencing
Gli protein, mouse
Medical Devices
Tandem Mass Spectrometry

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