Fig. 8

Reduced cholesterol in the cortex cerebri and hippocampus corresponds to areas with many NPC2-positive cells. The high occurrence of NPC2-positive neurons [visualized with neuronal nuclei antigen (NeuN) immunolabeling (red) and NPC2 immunolabeling (green)] observed in the cortex cerebri (a–i) and the CA3 region of the hippocampus (j–k) correspond with lower levels of cholesterol accumulation [visualized using Filipin staining (white)] in the high responder group of AAV-BR1-NPC2-treated Npc2−/− mice in both brain regions assessed. In comparison untreated Npc2−/− mice show extensive neuronal accumulation of cholesterol (only shown in high magnifications). Reduced cholesterol accumulation in the high responder AAV-BR1-NPC2-treated Npc2−/− mice is not limited to the NPC2 expressing cells, but also obvious in neighboring cells, suggesting uptake of secreted NPC2 in these cells, equivalent to cross-correction. Representative images from cortex cerebri and CA3 region of the hippocampus of the high responder group (n = 3). Scale bar = 25 µm