Skip to main content
Fig. 4 | Molecular Neurodegeneration

Fig. 4

From: Modifying Rap1-signalling by targeting Pde6δ is neuroprotective in models of Alzheimer’s disease

Fig. 4

REM modulates spatially discrete Rap1-ERK1/2 signalling processes. a Western blot analysis of ERK1/2 phosphorylation in neuroblastoma cells after 7 days with or without ATRA toxicity challenge and with or without (0.25 μM) REM (n = 3; Vehicle +/− ATRA: P = 0.0066; t = 5.191; DF = 4; Vehicle/REM + ATRA: P = 0.0052; t = 5.55; DF = 4). Representative Western blots are shown in inset above the graph. b Western blot analysis of ERK1/2 phosphorylation ratio to total ERK1/2 in DIV ≥19 mouse primary hippocampal neurons treated with or without 50 μM DHPG and REM/Vehicle as indicated (n = 6; ordinary two-way ANOVA followed by Tukey’s multiple comparison test; P < 0,0001; DF = 1; F (1, 20) = 27,41; vehicle +/− DHPG: P = 0,0248; q = 4,431; DF = 20; REM +/− DHPG: P < 0.0001; q = 14,9; DF = 20; vehicle/REM - DHPG: P = 0,0107; q = 4,975; DF = 20; vehicle/REM + DHPG: p = 0,0047; q = 5,497; DF = 20). Representative Western blot images are shown in insets above graph. c K+ current analysis in hAPP mice treated with a single dose of REM or vehicle show that application of REM increases the IA contribution at higher membrane potentials (50–60 mV) (n = 7 per condition; RM-two way ANOVA Interaction: P = 0.056; DF = 15; F(15,180) = 1.691; Sidak’s multiple comparison: membrane potential 50 mV Vehicle/REM: P = 0.0326; t = 3.122; DF = 192; membrane potential 60 mV Vehicle/REM: P = 0.0130; t = 3.401; DF = 192). d Analysis of AHP amplitudes in function of REM treatment obtained by longitudinal somatic recordings of single APs in WT and hAPP slices that were incubated with vehicle or 2 μM REM. (Two-way ANOVA repeated measures, followed by Sidak’s multiple comparison test; n = 7 WT mice or n = 8 hAPP mice; Treatment: P = 0.0015; DF = 1; F (1, 13)=15.91; Genotype: P = 0.0279; DF = 1; F (1, 13)=6.127; WT/APP + Vehicle: P = 0.0376; t = 2.502; DF = 26; hAPP + Vehicle/REM: P = 0.006; t = 3.635; DF = 13.) Examples of recorded traces are shown above the graph. e CA3-CA1 LTD: quantification of fEPSP slopes from hippocampal slices. Slices were continuously perfused with artificial CSF containing vehicle or REM for (at least) one hour prior to (pre-incubation), as well as during and after the addition of DHPG (two-way ANOVA repeated measures; n = 6 mice per condition; Treatment: P = 0.0032; DF = 1; F (1, 10)=14.91). Example traces are shown above the graph. f Graph shows the summary of mean fEPSP slopes during the 41–60 min interval from d (n = 6 mice per condition; P = 0.0008; t = 4.725; DF = 10)

Back to article page