Fig. 5

Opposing effects of ethanol and synaptamide on the cAMP system in LPS-induced neuro-inflammation. WT and GPR110 KO mice were given 3 g/kg ethanol through oral gavage and LPS (1 mg/kg, i.p.) was injected at 4 h after ethanol administration. Synaptamide (5 mg/kg, i.p.) was injected immediately after LPS administration. The expression of mRNA and protein in brain tissues was measured for isoforms of AC (ADCY) and pde4 at 2 and 24 h after LPS injection, respectively. The mRNA expression of ADCY8 (A) and PDE4B (B) were perturbed by LPS which was potentiated by ethanol. Synaptamide GPR110-dependently restored the reduced expression of ADCY8 caused by LPS and EtOH + LPS and reduced the PDE4B expression elevated by LPS and EtOH + LPS. The western blot analysis (C, D) showed an LPS-induced increase in PDE4B protein which was further elevated by ethanol pretreatment but was suppressed by synaptamide in a GPR110-dependent manner. Values are presented as mean ± SEM (n = 4 for A, B; n = 3 for C, D), representing two independent experiments. ns, the difference of means is not statistically significant. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 vs. Maltose group