Fig. 3: Kynurenine pathway activation and P2RX7 upregulation in Grk3^−/− mice.

Levels of (A) tryptophan (P = 0.094), (B) kynurenine (P = 0.014), (C) KYNA (P = 0.44), and (D) quinolinic acid (P = 0.12) in hippocampal tissue obtained from Grk3^−/− as compared to Grk3^+/+ mice. E Probenecid administration (200 mg/kg) was used to monitor accumulation of hippocampal KYNA (effect of: time F(12,108) = 11.47, P < 0.0010; genotype F(1,9) = 3.59, P = 0.091; interaction F(12,108) = 3.771, P < 0.0010) with significantly increased accumulation of KYNA in Grk3^−/− mice at 120 as well as 150 min post infusion (Bonferroni post hoc test, P = 0.0028 and P = 0.033, respectively). F Grk3^−/− mice displayed decreased expression of P2X7R on internal cellular membranes obtained from homogenized brain tissue (P = 0.017), while (G) no changes was observed in plasma membranes (P = 0.32). All experiments in (A)–(E) were carried out using 8 Grk3^+/+ mice and 7 Grk3^−/− mice. In (F) and (G) 5 Grk3^+/+ and 6 Grk3^−/− were used. Data in (A)–(D) and (F) to (G) were analyzed using Mann–Whitney U tests, while the data in (E) were analyzed using a 2-way repeated measures ANOVA followed by Bonferroni post hoc test. All error bars represent SEM. All tests were two-tailed. *P < 0.05, and **P < 0.01.