TSE Transmission to Sea Bream Figure 3. Progression of abnormal deposition in BSE-challenged fish. Sagittal brain sections from BSE-challenged fish taken at the indicated times p.i. were stained with H&E (A, D, G), or immunolabeled with SaurPrP1 (1:2000) without PK-digestion (B, E, H) and with PK-digestion (C, F, I). Images show diencephalon. The mean number of deposits (per section of fish containing deposits) observed in different brain regions without PK- treatment is indicated by the fill-type in the schematic drawings at the far left. Abbreviations as in Figure 2. The following areas were not examined: OB; OIN; OC; P. Rectangles indicate areas of magnification shown in the panels directly below. Arrowheads indicate the abnormal aggregates. Scale bars, 100 mm. doi:10.1371/journal.pone.0006175.g003 Given the morphological progression of the abnormal deposi- tion with time, it is tempting to hypothesize a scenario, in which the first type of aggregates (Fig. 8A, D, G, J) could have been the developmental ancestor of the second (Fig. 8B, E, H, K) and in which each may illustrate different stages of pathogenesis. The distention of axons and dendrites observed at 10 and 12 months p.i. reflects an initial neurodegenerative process in the brains of the BSE-challenged fish that may have been a very early reaction following exposure to the infectious agent. The complete destruction of the protective outer neurite layers, including the myelin sheath, followed by the disorganization of the microfila- ments and microtubuli could have subsequently created the first morphological type of aggregates initially detected at 16 and 18 months. These ‘‘pre-mature’’ deposits mainly consist of dystrophic PLoS ONE | www.plosone.org 5 July 2009 | Volume 4 | Issue 7 | e6175