Brain lesion and PrP^res deposit distribution of the TgVole (1x)-passaged recombinant PMSA products after secondary transmission in the same model.

Histopathological assessment of spongiform lesions and PrP^res deposits of TgVole (1x)-passaged PMSA preparations stMI-01, stMI-03, btMI-05, and btMI-09 after secondary transmission in TgVole (1x) shows clear spongiform changes upon hematoxylin and eosin staining (H&E). Micrographs of the temporal cortex and striatum of representative animals from each group are shown, notice intense spongiosis in the striatum in all groups, but only involvement of temporal cortex in the case of btMI-05. For stMI-01 and stMI-03-inoculated animals, in some animals from each group, a few small plaques in the hippocampus and granular-coalescent deposits in the striatum were detected (indicated by black arrowheads) but the phenotype was not homogeneous among the group. In contrast, btMI-05 and btMI-09-inoculated animals showed distinct patterns homogeneously observed in all animals within each group: btMI-05: granular to coalescent labeling associated with striatum vacuoles and intense plaque labeling in the hippocampus. btMI-09: fine punctate intraneuronal patterns with plaques mainly in the hippocampus (indicated by black arrowheads). Spongiform lesion profiles and PrP^res deposition profiles, shown on the right, represent the mean semi-quantitative scoring (0–4, vertical axis, ± standard error of the mean -error bars) of the spongiform lesions (continuous line, black) and the immunohistochemical labeling of PrP^res deposits (dashed line, black) across 14 brain regions (Pfc: piriform cortex, H: hippocampus, Oc: occipital cortex, Tc: temporal cortex, Pc: parietal cortex, Fc: frontal cortex, cc: corpus callosum; S: striatum, T: thalamus, HT: hypothalamus, M: mesencephalon, Mob: medulla oblongata, Cm: cerebellar nuclei, Cv: cerebellar vermis, Cc: cerebellar cortex). Overall, despite subtle differences detected between groups that could suggest that the four recombinant preparations might represent distinct strains, yet the presence of the most prominent lesions (such as focalized spongiosis in striatum or plaques in the hippocampus) in some animals across all groups may also argue in favor of a single or highly similar strain. H&E: Hematoxylin and eosin staining; IHC: Immunohistochemistry. (PDF)