Fig. 3: Reduced OPC-neuron contacts induce an accumulation of lysosomes and functional impairment in neurons.

A Immunostaining and quantification of lipid droplets in cortical neurons of control (ctl) and double knockout (dKO) mice with NeuN and BODIPY antibodies, respectively (4 mice per group). B Immunostaining and quantification of cFos⁺ cells in the whole brain of ctl and dKO mice (4 mice per group). C, D Dot plot of enriched gene ontology terms for biological processes (BP), cellular components (CC), molecular functions (MF), and KEGG pathways in genes from OPCs and neurons of dKO mice. E List of differentially expressed genes in OPCs and neurons of the dKO mice (M, bulkRNA-seq) and AD patients in early pathology (H, scRNA-seq). F, G Immunostaining and quantification of senescent neurons with NeuN and p16^INK4A (P16) at 12 months of age (ctl = 3 mice, dKO = 4 mice). H 3D reconstruction of OPCs immunolabelled with PDGFRα (Pα) at 6 months of age. I, J Morphological analysis of OPCs for the number of process intersections (I) and total process length (J) (ctl = 51 cells/3 mice, Tg2576 = 52 cells/3 mice). K Immunostaining and 3D reconstruction of OPCs (Pα), neurons (NeuN) and lysosomes (Cathepsin D, CSTD). L Quantification of the relative volume of OPC processes in contact with neuronal soma (ctl = 91 cells/3 mice, Tg2576 = 117 cells/3 mice) and the number of neuronal lysosomes (ctl=87 neurons/5 mice, Tg2576 = 115 neurons/5 mice). M, N Quantification of the relative mean distance between neuronal lysosomes and OPC surface (ctl = 91 cells/3 mice, Tg2576 = 117 cells/3 mice). M The size of the lysosomes is represented by the size of the filled circles, while the color indicates the frequency of each size in the total analysis. R.U. = relative units, normalized to the controls. Data are shown as mean ± SEM in (A, G, I, J, L, and N). Two-sided unpaired t test was used in (A, B, G, I, J, L, and N). Source data are provided as a Source Data file. Created in BioRender. Fang, L. (2025) https://BioRender.com/f32o880.