Fig. 6: A_2AR antagonism alleviates dopamine system changes in Gdnf ^{cHyper/cHyper};Nestin-Cre mice. See also Supplementary Figs. S7 and S8.

A Chord diagram depicting dopamine system-related genes differentially expressed in the prefrontal cortex (PFC), striatum (STR), or substantia nigra (SN) of Gdnf ^cHyper;Nestin-Cre mice. DE genes overlapping with those differentially expressed in Gdnf ^cHyper + AAV-Cre mice are shown with red arrows. Genes downregulated in Gdnf ^cHyper mice compared with wild-type controls are indicated with a blue bar and genes upregulated in Gdnf ^cHyper mice are indicated with a pink bar next to the name of the gene. WT, Gdnf ^wt/wt;Nestin-Cre; HET, Gdnf ^wt/cHyper;Nestin-Cre; HOM, Gdnf ^{cHyper/cHyper};Nestin-Cre. B Experiment schematic of A_2AR inhibition using istradefylline. BSL, baseline; VEH, vehicle. See Methods for details. C Average daily voluntary consumption of istradefylline-containing solution in the beginning (d1-d3), middle (d4-d7) and end (d8-d10) of the 10-day treatment period. Mean ± SEM. N = 5–7 mice per group. Two-way ANOVA Genotype × Period interaction. ***p < 0.001. D Striatal dopamine levels normalised to wild-type controls in Gdnf ^wt/wt;Nestin-Cre and Gdnf ^{cHyper/cHyper};Nestin-Cre before and after istradefylline treatment, measured with HPLC. Mean ± SEM. N = 5–13 mice per group. One-way ANOVA, Tukey’s multiple comparisons test. *p < 0.05; ***p < 0.001; n.s, not significant. E Similar to (D) but showing normalised dopamine levels in the prefrontal cortex. Mean ± SEM. N = 5–13 mice per group. One-way ANOVA, Tukey’s multiple comparisons test. **p < 0.01; n.s, not significant. F Striatal Gdnf mRNA levels in Gdnf ^wt/wt;Nestin-Cre and Gdnf ^{cHyper/cHyper};Nestin-Cre mice after istradefylline treatment. Mean ± SEM. N = 5–13 mice per group. One-way ANOVA, Tukey’s multiple comparisons test. **p < 0.01.