Fig. 1.

Effects of HDAC inhibitors, arimoclomol, and combined treatments on HSPA1A in motor neurons expressing TDP-43^G348C. (a) Phase contrast image of spinal cord-DRG culture. Arrows point to motor neurons. (b) Small but significant increase in the percentage of motor neurons with HSPA1A immunoreactivity 3 days following microinjection of plasmid encoding TDP-43^G348C, compared to absence of labeling in neurons injected with mCherry (control). (c)–(f) Percentage of HSPA1A immunopositive motor neurons after 3 days of treatment with vehicle, the HDAC inhibitors (c) SAHA, (d) RGFP109, (e) RGFP963 or (f) Tubastatin A, or with arimoclomol alone or in combination with the respective HDAC inhibitor. HDAC inhibitors with class I activity (c)–(e) significantly increased the percentage of neurons expressing HSPA1A. Arimoclomol and the HDAC6 inhibitor Tubastatin A were ineffective. Data presented as mean ± SD. Each data point on the graph represents the mean % of neurons expressing HSPA1A in each of 9 cultures (11–49 neurons/culture). Statistical significance was evaluated by one-way ANOVA followed by Bonferroni post hoc analysis. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Scale bar = 20 μm. Abbreviations used: DRG, dorsal root ganglia; HDAC, histone deacetylase; SAHA, suberoylanilide hydroxamic acid; SD, standard deviation; TDP-43, TAR DNA binding protein 43 kDa.