FIGURE 1.

Induction of HDAC1 expression in vulnerable brain region in mouse models of neurodegenerative disease. A, Western blot analysis of lysates from the striatum (St.) or extra-striatal tissue (EST) of R6/2 mice at 6, 9, and 13 weeks were analyzed for expression of HDAC1 or tubulin as loading control. B, in the CaMK/p25 transgenic line, p25-GFP expression is driven through a doxycycline-inducible CaMK promoter. Left panel, expression of p25-GFP transgene is observed only when its expression is induced and in the cortex and hippocampus where the CaMK promoter is active. Right panel, HDAC1 expression is elevated in cortex and hippocampus, but not in cerebellum. Lysates for both panels were from mice in which transgene expression was induced for 8 weeks at which time neurodegeneration is obvious in the cortex and hippocampus (our observations and Ref. 23). Tg-ON, transgenic mice taken off the doxycycline-containing food; Tg-OFF, transgenic mice kept on the food. C, lysates from CGN cultures treated with either HK or LK for 6, 9, 12, or 15 h were subjected to Western blotting and probed for HDAC1. The blot was reprobed with tubulin to show equal loading. The lack of alterations in HDAC1 expression was confirmed in multiple experiments. D, cultured cortical neurons were either left untreated or treated with HCA for 3, 6, 9, 12, or 15 h, and the lysates were subjected to Western blotting and probed for HDAC1. The blot was reprobed with tubulin to show equal loading. The absence of major alterations in HDAC1 expression was confirmed in additional experiments.