FIGURE 2.

Diverse HD models demonstrate altered sensitivity to MT depolymerization. A, primary striatal neurons from HD mice (HD94) are more resistant to colchicine-induced toxicity than control neurons. After 16 days in vitro (DIV16) neurons were administered colchicine (10 μm) or vehicle (DMSO) and cell death was assessed 96 h later (see “Experimental Procedures”). Colchicine was significantly less toxic to HD94 neurons (analysis of variance, p = 0.0006) (*, p < 0.05). B, B27 (medium supplement) withdrawal is more toxic in HD94 neurons than control neurons: medium from DIV14 neurons was exchanged with complete medium or medium lacking B27, and assessed for cell death 48 h later. Fisher post hoc analysis revealed that under complete medium (CM), cell death was comparable in control (Ctrl) and HD94 neurons (p = 0.3276). B27 withdrawal decreased viability in both genotypes (p < 0.0001); however, it was significantly more toxic in HD94 neurons than control (*, p = 0.0074). C, medium from DIV14 neurons was exchanged with medium lacking B27 in the presence or absence of colchicine (0.1 μm) and cell viability was assessed 48 h later. Viability is shown relative to DMSO-treated cells. Analysis of variance revealed B27 withdrawal induced toxicity was significantly (*, p < 0.05) suppressed by colchicine treatment in HD94, but not in control neurons. D, immortalized striatal neurons from HD knock-in mice (WT, STHdh^Q7, and mutant, STHdh^Q111) were treated with DMSO or various MT inhibitors, each at 2.5 μm, and cell viability was determined after 24 h using a luminescence-based ATP assay (see “Experimental Procedures”). Cell viability was normalized to DMSO-treated STHdh^Q7 and STHdh^Q111 cells and the data are the mean ± S.E., of an experiment performed in triplicate. E, STHdh^Q7 and STHdh^Q111 were treated with a dilution series of colchicine, Pdx, etoposide, or Taxol and viability was determined as in D. Data are the mean ± S.E. of an experiment performed in triplicate (*, p < 0.05 Student's t test).