Fig. 1.

Biphasic response of alpha-synuclein immunoreactivity following SARS-CoV-2 infection. (a). Schematic representation of the coronal hamster brain sections that were stained, red dots highlighting the regions of interest examined (Olfactory bulb glomerular, granular and external plexiform layers (bulbus_glom, gran, EPL), caudate putamen (cpu), cingulate cortex (ctx_cg), basolateral amygdala (bla), ca1 region of hippocampus (hippoc-ca1), and aud, v2m and pir regions of cortex, substantia nigra partes reticulata and compacta (SNR, SNC)). Modification of coronal brain illustrations of Wood et al., 2001.¹²¹ b. Representative histological stainings of aSyn recorded at a 10× magnification (i-ii, iv-v) and confocal laser scanning macroscopy at 160× (iii, vi) in the cortex from female animals with PBS or SARS-CoV-2 infection at 6 and 21 dpi. Scale bar in widefield images = 200 μm, in confocal images = 10 μm. The viridis lookup table was used for the histological images to increase the visibility of expression changes. (c) Group mean of the normalized aSyn-IR per region in sex/infection groups demonstrating the general biphasic tendency of the aSyn response to infection. (d) Heatmaps of group mean normalized aSyn-IR per brain region in female and male animals in the three groups PBS, 6 dpi and 21 dpi. (e) Distribution of brain regions where PBS and SARS-CoV-2 groups differ significantly. Statistics: fishers exact test between male and female groups at 6 and 21 dpi. (f–g) Quantification of mean aSyn-IR in relevant regions for female (f) and male (g) hamsters. Data normalized to female and male PBS control group. Circles depict individual animals. The mean ± SEM is additionally shown. Mark the different scales on the y-axes. Mixed-effect analysis of aSyn-IR across brain regions in female (f) and male (g) hamsters evaluating effects of region and infection followed by a Dunnett's multiple comparisons test to evaluate infection effects within brain regions. Further information on Mixed-effect statistics can be found in Supplementary data file 1. Differences are depicted as ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Sample sizes are shown at the bottom of the groups in the graphs. No experimental outliers were excluded, group differences originate from apriori quality control.