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. 2021 Sep 26;9:158. doi: 10.1186/s40478-021-01262-y

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© The Author(s) 2021

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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — Hematoxylin and Eosin (H&E) staining and PrP immunohistochemistry (IHC). a, H&E (upper panels) & IHC (lower panels) staining of brain sections of TgVV mice inoculated with sPMCA-generated CWD-derived human PrP^Sc (Cd-HuPrP^Sc). Upper left panel: Spongiform degeneration (SD) preferentially affecting the deep layers of the cerebral cortex (CC). Upper right panel: Cortical eosinophilic plaque surrounded by vacuoles; inset: PrP IHC of the plaque shown in the upper right panel; the rim of the plaque was more heavily stained than its core. Lower left panel: PrP granules (arrowhead) accumulating mainly in the deep cortical layers. Lower right panel: Granular PrP inside and around the perikarya and processes (arrow) and plaque-like PrP deposits (arrowhead). b, H&E (upper panels) & IHC (lower panels) staining of brain sections of TgMM mice inoculated with sPMCA-derived human CWD prions. Upper left panel: SD (arrow) affecting less severely CC than thalamus (Upper right panel); inset in Upper left panel: higher magnification of SD. Lower left panel: Granular PrP deposits affecting the thalamus; Lower right panel: Pattern of PrP deposition similar to those shown in TgVV mice (Lower left panel in a) affecting the ventral midbrain. Bar size: 50 µm; antibody: 3F4. c, Profiles of brain distribution and severity of SD in the two Tg mouse lines challenged with Cd-HuPrP^res were virtually identical, except for more severe lesions in the CC of TgVV mice. d, More severe lesions correlated with the presence of PrP plaques in TgVV mice; *P < 0.05–0.03, ***P < 0.006. HI: hippocampus, BG: basal ganglia, TH: thalamus, dMB and vMB: dorsal (d) and ventral (v) midbrain (MB), BS.i.: brainstem, inferior, CE: cerebellum. PrP pl.: PrP plaques; w/o: without. Each point of the lesion profile was expressed as mean ± standard error of the mean. Statistical significance was determined by a two-tailed Student’s t-test