Figure 2.

LM22A-4 reduces diffuse and aggregated huntingtin in nuclei of striatal and cortical neurons of R6/2 mice. A, Representative photomicrographs showing nuclear huntingtin immunostaining in striatum of R6/2 mice treated with vehicle (Veh; top) or LM22A-4 (LM-4; bottom). Diffuse huntingtin immunostaining was lighter and surrounded the huntingtin aggregates (arrows), which appeared smaller and less numerous in R6/2 mice given LM-4 (n = 9 mice) compared with those given Veh (n = 7 mice). Scale bar, 5 μm. Quantitative analyses of a sample field (0.063 mm²) in striatum (Str) and cortex (Cx) of one section per mouse confirmed these observations. B, The total area, number, and intensity of nuclei containing diffuse huntingtin staining decreased with LM-4 treatment in both brain areas (⁺p ≤ 0.05, ⁺⁺p ≤ 0.01, and ⁺⁺⁺p ≤ 0.001 vs R6/2 veh). C, The total area occupied by huntingtin aggregates was reduced in Str and Cx due to a decrease in aggregate number and size (⁺p ≤ 0.05, ⁺⁺p ≤ 0.01, and ⁺⁺⁺p ≤ 0.001 vs R6/2 veh). Results are normalized to the R6/2 vehicle group and expressed as mean ± SEM. Statistical significance was determined with a two-tailed Student's t test.