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. 2014 Jun 23;111(27):9947–9952. doi: 10.1073/pnas.1309426111

Fig. 4.

Fig. 4.

Clenbuterol-mediated restoration of brain growth factor expression and synergistic effects with rhIGF1 in male Mecp2-null mice. (A–C) Graphs showing sample-by-sample correlation between (A) BDNF mRNA and LIN28A protein levels, (B) mature let-7f miRNA levels with LIN28A protein, as well as (C) IGF1 mRNA expression. Colors depict sample identity [blue for WT (v), green for KO (t), and red for KO (v) mice]. (D) Schematic depicting the proposed molecular mechanism linking Mecp2-regulated BDNF to IGF1 through LIN28A and IGF1. The effect of clenbuterol treatment in restoring NGF and BDNF levels through CREB activation and indirectly affecting IGF1 expression, thus regulating growth factor-mediated functions, is also shown. (E) Graph showing cumulative survival distributions for Mecp2 KO mice receiving clenbuterol and rhIGF1 cotreatment [KO (Clen + IGF1), blue circles]. Survival of KO vehicle [KO (v), open red circles] and clenbuterol-treated [KO (clen), open green circles] mice is also depicted for comparison (from Fig. 1A). The stars represent statistical significance based on Gehan–Breslow–Wilcoxon test (***P < 0.001, *P < 0.05).