Skip to main content
. 2015 Nov 11;35(45):15073–15081. doi: 10.1523/JNEUROSCI.1087-15.2015

Figure 4.

Figure 4.

Elevated protein synthesis in Syngap+/− hippocampus is corrected by inhibitors of mGluR5 and Ras–ERK1/2 signaling. A, schematic of the drug targets for CTEP, lovastatin, and U0126, each shown previously to reduce Ras–ERK1/2 activation and correct basal protein synthesis in Fmr1−/y mice. B, CTEP (10 μm) reverses elevated protein synthesis in Syngap+/− mice (WT, vehicle, 100 ± 3%; CTEP, 106 ± 5%; Syngap+/−, vehicle, 124 ± 5%; CTEP, 102 ± 8%; n = 9; ANOVA, genotype, p = 0.0007; KO treatment, p = 0.0014). Ci–Ciii, Lovastatin (100 μm) reverses elevated protein synthesis (Ci) in Syngap+/− mice (WT, vehicle, 100 ± 4%; lovastatin, 93 ± 7; Syngap+/−, vehicle, 142 ± 9%; lovastatin, 106 ± 8%; n = 7; ANOVA, genotype, p = 0.0061; KO treatment, p = 0.013). Example Western blot (Cii) and quantification of ERK1/2 activity (Ciii) in vehicle- and lovastatin-treated hippocampal slices revealed lovastatin significantly reduces phosphorylation levels of ERK1/2 in Syngap+/− mice (phosphorylated/total ERK1/2, WT, vehicle, 100%; Syngap+/−, vehicle, 140 ± 6%; WT, lovastatin, 100 ± 8%; Syngap+/−, lovastatin, 106 ± 11%; n = 10; ANOVA, genotype, *p = 0.0086; KO treatment, p = 0.0057). The gray line to the left of the lovastatin-treated Syngap+/− Western blot indicates that this lane was not adjacent to each of the other three lanes, but was run on the same gel, and hence was processed identically. D, U0126 (5 μm) reverses elevated protein synthesis (Di) in Syngap+/− mice (WT, vehicle, 100 ± 4%; U0126, 98 ± 8%; Syngap+/−, vehicle, 134 ± 9%; U0126, 102 ± 9%; n = 9; ANOVA, genotype, p = 0.003; KO treatment, p = 0.004). Example Western blot (Dii) and quantification (Diii) of ERK1/2 activity in vehicle- and U0126-treated hippocampal slices show U0126 abolishes ERK1/2 activity in both WT and Syngap+/− mice (phosphorylated/total ERK1/2, WT, vehicle, 100%; Syngap+/−, vehicle, 165 ± 15%; WT, lovastatin, 10 ± 3%; Syngap+/−, lovastatin, 13 ± 3%; n = 5; ANOVA, genotype, p = 0.0054; WT treatment, p = 0.005; KO treatment, p = 0.0002). *p < 0.05; **p < 0.01; ***p < 0.001.