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. 2012 Nov 12;122(12):4344–4361. doi: 10.1172/JCI65053

Figure 6. Calpain and PARP inhibitors suppress striatal degeneration and improve motor impairments in Mth1/Ogg1-DKO mice induced by 3-NP.

Figure 6

(A) MDL-28170 (MDL), a cell-permeable calpain inhibitor, and 3-AB, an inhibitor of PARP, efficiently prevented 3-NP–induced motor impairments in DKO mice. Numbers of animals examined per condition are 7 (3-NP + PBS), 6 (3-NP + MDL), and 9 (3-NP + 3AB). (B) MDL or 3-AB suppressed loss of MSNs by 3-NP. DARPP32-positive cells (red) were detected. Scale bar: 50 μm. (C) MDL and 3-AB significantly suppressed loss of DARPP32-positive cells by 3-NP. Numbers of animals examined per condition are 4 (PBS), 4 (3-NP + PBS), 6 (3-NP + MDL), and 6 (3-NP + 3AB). Data are shown as LS means ± SEM. (D) MDL or 3-AB effectively diminished microgliosis. F4/80-positive cells (dark blue) were detected. Scale bar: 50 μm. (E) Calpain inhibitor inhibits perinuclear distribution of α-spectrin. Arrows, altered localization of α-spectrin. Scale bar: 50 μm. (F) The PARP inhibitor suppresses PAR/AIF. Scale bar: 50 μm. In A and C, the results of 1-way ANOVA are shown. *P, compared with 3-NP + PBS (Hsu’s MCB test).