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. 2020 Aug 9;140(4):513–534. doi: 10.1007/s00401-020-02193-z

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — AL002a -treated mice show increased OPC density, mature myelin and remyelination after CPZ-induced demyelination. a Representative images of PDGFRα⁺ (red) and DAPI (blue) in the CC at WK 4 + 3D and WK 4 + 7D. Original magnification, × 20. Scale bar, 400 µm. Insert magnification, × 60. Scale bar, 25 µm. b Quantification of PDGFRα⁺ cell density. CTR group: WK 4 + 3D N = 6 mice, n = 24 fields; WK 4 + 7D N = 5, n = 20; AL002a-treated group: WK 4 + 3D N = 6, n = 24; WK 4 + 7D N = 5, n = 20; **P ≤ 0.01; ****P ≤ 0.0001; WK 4 + 3D two-tailed Mann–Whitney test; WK 4 + 7D two-tailed unpaired Student’s t test. c Representative images of OLIG2 (green), CNPase (red) and DAPI (blue) in the CC at WK 4 + 3Ds and WK 4 + 7D. Original magnification, × 10. Scale bar, 200 µm. Insert magnification, × 60. Scale bar, 25 µm. d Quantification of the density of OLIG2⁺ cells at both the time points. e Quantification of the percentage of CNPase⁺ staining in the CC. CTR group: WK 4 + 3D N = 6, n = 12; WK 4 + 7D N = 5, n = 10; AL002a-treated group: WK 4 + 3D N = 5, n = 10; WK 4 + 7D N = 4, n = 8; *P < 0.05, **P ≤ 0.01; two-tailed unpaired Student’s t test. RT-qPCR quantification of mRNA levels of myelin basic protein (Mbp) (f), myelin oligodendrocyte glycoprotein (Mog) (g) and proteolipid protein 1 (Plp1) (h) in the corpus callosum (CC) and the hippocampus (HP) of Trem2^+/− mice treated with AL002a antibody or CTR. Tissues were collected at WK 4 + 7D. CTR group: N = 5, AL002a-treated group: N = 5 (Mpb); N = 4 (Mog); N = 3 (Plp1). *P < 0.05, two-tailed unpaired Student’s t test. i Electron microscopy (EM) of a naïve mouse and mice treated with AL002a or isotype control antibody at WK 4 + 3D and WK 4 + 7D. Green plus sign indicates myelinated axons and red minus sign indicates naked axons. Original image = × 5000. Scale bar = 2 µm. j Percentage of myelinated axons (MA) and naked axons (NA) in naïve mice, and in CTR and AL200a-treated mice at WK 4 +3D and WK 4 + 7D. ***P < 0.001 at WK 4 + 3D and ****P < 0.0001 at WK 4 + 7D, two-tailed Mann–Whitney test. k G-ratio of myelinated fibers in naïve mice, and in CTR and AL002a-treated mice at WK 4 + 3D and WK 4 + 7D. Each dot represents one axon. Naïve mice N = 2, CTR treated mice at WK 4 + 3D N = 5 and at WK 4 + 7D N = 5; AL002a-treated mice at WK 4 + 3D N = 4 and at WK 4 + 7D N = 5. ***P < 0.001 at WK 4 + 3D and ****P < 0.0001 at WK 4 + 7D, two-tailed unpaired Student’s t test