ICRF-193-mediated TOP IIβ inhibition in SN results in loss of nigro-striatal projection. A. Photomicrographs of TH-immunostained sections of SN of the 2-month-old mice treated with 2 μl 50 μM ICRF-193 (a) and vehicle (b) for 2 weeks. C. Photomicrographs of TH-immunostained sections of striatum of the 2-month-old mice treated with 2 μl ICRF-193 (a) and vehicle (b) for 2 weeks. B. and D. Quantitative analysis of the number of TH+ neurons or optical density of striatal TH+ fibers in the right SN (B) or striatum (D). E. Effect of ICRF-193 on nigra-striatum pathway maintenance. SN neurons were labeled by stereotaxic injections of Fluorogold two weeks after ICRF-193 or vehicle treatment. F. Statistic analysis showed that the number of Fluorogold labeled dopaminergic neurons was robustly decreased after ICRF-193 injection. G. Effect of ICRF-193 on neural transmitter release of dopaminergic neurons. Striatal DA, its metabolite DOPAC and 5-HIAA concentrations were tested by HPLC. The results above are expressed as means ± SEM of 4 mice in each group. *p < 0.05 and **p < 0.01 vs. vehicle control. Arrows show the injection side. Scale bar = 100 μm.