Pharmacological treatment modulates the level of TMH-H3 (K9) in R6/2 mice. (A) The TMH-H3 (K9) immunoreactivity in striatal neurons was markedly increased in R6/2 mice (b) compared with WT mice (a). Polytherapy attenuated the TMH-H3 (K9) immunoreactivity (c). (Magnification, ×10; scale bar, 200 μm.) (B) Combined mithramycin and cystamine treatment reduced mtHtt aggregates and sequestration of TMH-H3 (K9) by mtHtt in R6/2 mice. (a, d, and g) MtHtt (green). (b, e, and h) TMH-H3 (K9) (red). (c, f, and i) Overlay images. (C) Mithramycin and cystamine combinational treatment significantly reduced the level of TMH-H3 (K9) in R6/2 mice. The level of TMH-H3 (K9) was normalized to total histone H3 level. (D) Densitometric analysis of TMH-H3 (K9) protein levels from the data in C. ∗, Significantly increased compared with WT at P < 0.05; #, significantly decreased compared with vehicle-treated R6/2 mice at P < 0.05.