Figure 1.

Age-related changes of myelin sheath and oligodendrocyte lineage cells in CNS. (A) Representative DTI-based white matter mapping images from young and aged adults. With the presented color-coding, red represents fibers crossing from left to right, green crossing in the posterior anterior direction, and blue crossing in the inferior–superior direction. (B) Comparison of DTI derived metrics between young and aged adults (****P-value < 0.0001 by student’s t test). (C) Linear regression plot showing the change in radial diffusivity with age (P-value < 0.0001). (D) Representative confocal microscopic images and quantification of mean MBP intensity (**P-value < 0.01 by student’s t test, n = 5 samples per condition). Scale bar: 50μm. (E) Representative TEM images in the external capsule for young and aged mice. Red asterisks and red arrows showing myelin thickness changes of axons with similar diameters, respectively. Scale bar: 2μm. Violin plots showing the g ratio of myelinated axons in aged mice versus young mice (****P-value < 0.0001 by student’s t test. The numbers of axons from four mice are indicated). Scatterplots depicting the g ratio as a function of axon diameters. (F) Representative confocal microscopic images in young and old cortex staining for PDGFRA and CC1. Scale bar: 100μm. Bar plots depicting the quantification of PDGFRA+ and CC1+ cells (** P-value < 0.01 by student’s t test. n = 5 samples per condition). (G) T-distributed stochastic neighbor embedding (t-SNE) projection of OPCs and OLGs from young and aged mice. (H) Gene ontology (GO) enrichment network plot was achieved using Metascape. Two gene lists of DEGs between aged and young OPCs or OLGs were submitted. The significantly overexpressed GO terms were grouped into several clusters based on their membership similarity. The contribution percentage of different cells was shown in each GO node. (I) Sankey diagram showing the interactions between resident cells in brain and OPCs or OLGs on GO term immune response (GO:0006955). The proportional flow represented the number of gene pairs.

Abbreviations: CNS, central nervous system; FA, fractional anisotropy; MD, mean diffusivity; AD, axial diffusivity; RD, radial diffusivity; OPCs, oligodendrocyte precursor cells; OLGs, oligodendrocytes; MG, microglia; EC, endothelial cells; MAC+ImmN, macrophages and immature neurons; ASC, astrocytes; EPC, ependymocytes; mNEUR, mature neurons; MBP, Myelin basic protein; WB, whole brain; DTI, diffusion tensor imaging; TEM: Transmission electron microscopy.