Figure 5

Proposed paclitaxel chemotherapy-induced reduction in neurogenesis. This schematic drawing indicates that chemotherapy-induced reduction in neurogenesis is caused by reduction of vesicular zinc after axonal transport blockade. (A) Normal axonal flow. Physiologically healthy neurogenesis ordinarily occurs under conditions where cytoplasmic and vesicular zinc are regulated by axonal flow. (B) Axonal flow is inhibited by paclitaxel. Anterograde and retrograde axonal flow of zinc is blocked by paclitaxel. Reduced vesicular zinc by paclitaxel may decrease hippocampal neurogenesis. Under chemotherapy (Px), hippocampal zinc may be excluded from the synaptic vesicle, thus promoting a zinc deficient-like state. Taken together, CICI may arise due to an acute decrease in neurogenesis caused by inhibition of ZnT3-dependent vesicular zinc transport.