Human neural stem cells restore spatial memory in a transgenic Alzheimer’s disease mouse model by an immunomodulating mechanism

• DOI: 10.3389/fnagi.2023.1306004
• Publication Date: 2023-12-14T14:06:05Z
• Authors: Kevin S. Chen; Mohamed H. Nourel...; Lisa M. McGinley; John M. Hayes; Diana M. Rigan; Jacquelin F. Kwentus; Shayna N. Mason; Faye E. Mendelson; Masha G. Savelieff; Eva L. Feldman
• Keywords: Amyloid (mycology)

Introduction Stem cells are a promising therapeutic in Alzheimer’s disease (AD) given the complex pathophysiologic pathways involved. However, mechanisms of stem remain unclear. Here, we used spatial transcriptomics to elucidate human neural (hNSCs) an animal model AD. Methods hNSCs were transplanted into fimbria fornix hippocampus using 5XFAD mouse model. Spatial memory was assessed by Morris water maze. Amyloid plaque burden quantified. performed and differentially expressed genes (DEGs) identified both globally within hippocampus. Subsequent pathway enrichment ligand-receptor network analysis performed. Results hNSC transplantation restored learning curves mice. there no changes amyloid burden. showed 1,061 DEGs normalized hippocampal subregions. Plaque induced microglia, along with populations stage 1 2 associated microglia (DAM), upon transplantation. Pathologic signaling between DAM also restored. Discussion many dysregulated genes, although this not mediated change levels. Rather, appear exert beneficial effects part modulating microglia-mediated neuroinflammation