Fig. 4.

Only fibrillar αSynuclein variants induce progressive DA neuron degeneration in vivo. a–i Representative images illustrating nigral DA neurodegeneration and significant overexpression of αSynuclein in the injected hemispheres by double staining for TH (red) and αSynuclein (green). Each column contains rostral-to-caudal coronal sections taken from the same animal and gives an overview of the extent of nigral DA neuron loss induced by expression of WT (d–f) or TP (g–i) αSynuclein at 14 weeks after AAV injection. Non-transduced control sections are shown in a–c. Higher magnification images (j, k) are optical sections of 1 μm and were generated with an ApoTome. DA cell bodies which demonstrated immunoreactivity for both, the DA marker TH and human αSynuclein, were found more frequently for TP than for WT. (l) Representative image of a coronal section showing nigral degeneration in a AAV-WT αSynuclein-injected animal. The nigral DA neurons were specifically labeled with an antibody against VMAT2 and with standard DAB immunohistochemistry. The expression of WT αSynuclein led to loss of VMAT2-positive neurons in the SNpc, compared with the contralateral intact side. m Changes in total number of VMAT2-positive cells in SNpc over time, as determined by stereology in the AAV-αSynuclein-WT, A30P, A56P, TP and AAV-EGFP-injected rats (n = 5–6 animals per time point and group). Data are shown as mean 

±

 SD; significant differences between groups outlined below the graph (Tukey’s test)