Fig. 5: Striatal elevation of endogenous GDNF in adults induces cortical hypodopaminergia. See also Supplementary Fig. S6.
A Schematic of adult-onset upregulation of endogenous GDNF using AAV-Cre. B Striatal Gdnf mRNA levels measured with qPCR. Box plots show median, upper, and lower quartiles, as well as maximum and minimum values. N = 7–8 mice per group. One-way ANOVA, Tukey’s multiple comparisons test. *p < 0.05; ***p < 0.001. C Striatal dopamine release in response to burst stimulus, relative to single stimulus, measured by fast-scan cyclic voltammetry. Box plots show median, upper and lower quartiles, and maximum and minimum values. n = 10–11 striatal slices (from N = 6 mice) per group. Unpaired t-test. *p < 0.05. D Total tissue dopamine levels in the PFC, measured with HPLC. Box plots show median, upper, and lower quartiles, as well as maximum and minimum values. N = 6–8 mice per group. One-way ANOVA, Tukey’s multiple comparisons test. *p < 0.05. E Top enriched non-redundant GO biological process categories of DE genes in the PFC of Gdnf wt/cHyper mice compared to Gdnf wt/wt mice. F Similar to (D) but showing top enriched categories between Gdnf cHyper/cHyper and Gdnf wt/wt mice. G Venn diagram indicating overlapping DE genes in the PFC between Gdnf cHyper;Nestin-Cre and Gdnf cHyper + AAV-Cre mice. Genes differentially expressed in either heterozygous or homozygous mice compared to wild-type controls are shown. H Venn diagrams indicating overlapping DE genes in the PFC between post-mortem human PFC RNAseq datasets originating from the Harvard Brain Bank and Charing Cross Hospital, and Gdnf cHyper;Nestin-Cre mice. I Similar to (G) but showing the overlap between human datasets and Gdnf cHyper + AAV-Cre mice.
