Figure 4. TSA administration in Smn^2B/− mice reversed both proteasomal and autophagosomal atrophy.

(a) Mice were treated with either DMSO or TSA daily from P3 to P21, and then sacrificed for analysis. DMSO-treated Smn^2B/− mice were significantly smaller in weight compared to control mice (p ≤ 0.001). TSA-treated mutant mice showed a significant increase in weight compared to DMSO-treated Smn^2B/− mice (p ≤ 0.01), although they never reached the weight of controls animals. (b) Atrogin-1 and MuRF1 E3 ligase transcript levels were significantly higher in muscles from Smn^2B/− mice compared to control counterparts (p ≤ 0.01 and p ≤ 0.05 respectively). However, this increase was attenuated in TSA-treated Smn^2B/− mice (p ≤ 0.01 and p ≤ 0.05 respectively). (c) TSA treatment of Smn^2B/− mice resulted in a decrease in the level of ubiquitinated proteins towards control levels. (d) Gabarapl1, CathepsinL and Bnip3 mRNA levels in muscles of Smn^2B/− mice were restored to control levels upon TSA treatment. (e,f) LC3-II and P62 protein levels in Smn^2B/− mice dropped to control levels upon TSA treatment. (N = 3 for all experiments except c (Smn^2B/− TSA N = 4); p ≤ 0.05 for *, p ≤ 0.01 for **, and p ≤ 0.001 for ***).