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. 2021 Jan 15;11:589471. doi: 10.3389/fneur.2020.589471

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Copyright © 2021 Zareba-Paslawska, Patra, Kluzer, Revesz and Svenningsson.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The tau pathology transmission in oligodendrocytes. (A) The microphotography pictures of double immunohistochemistry staining of tau phosphorylated at Ser202 (CP13 antibody, brown chromogen) in oligodendrocytes (Olig2, nuclear marker, red/pink chromogen). The cell distribution in the contralateral (left panel) and ipsilateral side (right panel) of the striatum (left subpanel) and corpus callosum (right subpanel) after 1 month (upper panel) and 12 months (lower panel) of control-tau (upper subpanel) or CBD-tau (lower subpanel) inoculation. The representative pictures of cells in each group are presented as the black bordered inserts. The presence of pathological tau in oligodendrocytes increases upon CBD-tau inoculation at 12 months postsurgery. No changes for control-tau were observed. The scale bar represents 50 μm and applies to all pictures; the black-bordered inserts represent 4× digital enlargement. (B–I) the quantitative analysis of double positive oligodendrocytes (CP13⁺/Olig2⁺): 1 month postsurgery in the contralateral (B, controls n = 3, CBD n = 8) and ipsilateral (C, controls n = 4, CBD n = 8) striatum; 12 month postsurgery in the contralateral (D, controls n = 6, CBD n = 4) and ipsilateral (E, controls n = 4, CBD n = 4) striatum; 11 months postsurgery in the contralateral (F, controls n = 3, CBD n = 7) and ipsilateral (G, controls n = 4, CBD n = 7) corpus callosum; and 12 month postsurgery in the contralateral (H, controls n = 5, CBD n = 4) and ipsilateral (I, controls n = 4, CBD n = 4) corpus callosum. The significant increase of tau phosphorylated at Ser202 positive oligodendrocytes in CBD-tau injected animals was observed in striatum and corpus callosum 12 months postsurgery compared to control-tau animals. (J–L) the correlation of double-positive oligodendrocytes (CP13⁺/Olig2⁺) as a fraction of all oligodendrocytes between the corpus callosum and striatum (J), between the ips- and contralateral side of CBD-tau (K) and control-tau (L) injected animals. The striatum and corpus callosum transmissible changes in oligodendrcytic tau pathology were detected by the presence of the significant positive correlation between them (J). The significant positive correlation between ipsi-and contralateral hemispheres of oligodendrcytic tau pathology was observed only in CBD-tau (K), and not control-tau (L) injected animals strengthening that only pathological tau is able to trigger transmissible changes in oligodendrocytes across hemispheres. Comparison between 2 groups was performed using the Mann–Whitney U test. Spearman's rank correlation coefficient was used to analyze dependence between 2 sets of data. P value < 0.05 was considered statistically significant. *P < 0.05.