Brain lesion and PrP^res deposit distribution in TgMoL108I mice inoculated with btMI-09 prion sequentially adapted across cofactor-devoid and dextran sulfate-complemented PMSA substrates.

Histopathological assessment of spongiform lesions and PrP^res deposits of TgMoL108I mice inoculated with the PMSA preparations btMI-09 dex, btMI-09 CB, btMI-09 dex², and btMI-09 CB². These preparations are products of the sequential adaptation of the original btMI-09 dex recombinant prion in cofactor-devoid and dextran sulfate-complemented PMSA substrates. The assessment aimed to compare the pathobiological features of all four preparations. <b>A)</b> Hematoxylin and eosin staining (H&E) shows moderate spongiform lesions in the thalamus and absence of spongiosis in the cerebellar cortex. The pattern of PrP^res deposits, labeled with 2G11 monoclonal antibody (1:100), reveals PrP^res small aggregates in the thalamus (indicated by black arrowheads) and larger plaques, characteristically located in the white matter of the cerebellar cortex. Spongiosis distribution profiles and PrP^res deposition profiles for each group, shown below, 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. <b>B)</b> Spongiform lesion and PrP^res deposit profiles plotted together (btMI-09 dex in yellow, btMI-09 CB in grey, btMI-09 dex² in black, and btMI-09 CB² in black) illustrate the high similarity of localization and intensity of the spongiform lesions and PrP^res deposits in all cases. This suggests no significant alteration of the pathobiological features of the original btMI-09 preparation in this model occur related to the presence or absence of the cofactor in the propagation environment. H&E: Hematoxylin and eosin staining; IHC: Immunohistochemistry. (PDF)