Figure 1.
Phenotypic correction by genotype correction of DYRK1A copy number.
Wild type (WT), YACtg152F7 transgenic (TG), dyrk1a (+/−) (HT) and double transgenics (TGxHT) generated by three different crossings. A: brain DYRK1A mRNA levels determined by quantitative PCR; B: in vivo MRI assessment of total brain volume (mm3); ** for p<0.01. (Mann-Whitney-Wilcoxon test; statistical significance considered to be p<0.05); C: linear regression analysis of brain volume and DYRK1A gene dosage. (R2 = 0.977).
Figure 2.
Average DYRK1A protein levels in thalamus-hypothalamus for each genotype-treatment group.
A: western blot assessment of dyrk1a and actin levels; B: average Dyrk1a protein levels for wild type (WT, n = 6), YACtg152F7 transgenic (TG, n = 6) water-fed (H2O) and in wild type (WT, n = 3), YACtg152F7 transgenic (TG, n = 7) green tea-fed (GTP). ** for p<0.01.
Figure 3.
Effect of GTP treatment on DYRK1A-induced brain alterations.
A: weight of total brain (mg) in wild type (WT, n = 26), YACtg152F7 (TG, n = 13) water-fed (H2O) and in wild type (WT, n = 13), YACtg152F7 transgenic (TG, n = 18) green tea-fed GTP; B: in vivo MRI assessment of total brain volume (mm3) in wild type (n = 10) and YACtg152F7 transgenic (n = 10) water-fed (H2O) and in wild type (n = 9) and YACtg152F7 transgenic (n = 11) green tea-fed GTP; C: in vivo MRI assessment of hypothalamus-thalamus volume (mm3) in wild type (n = 6) and YACtg152F7 transgenic (n = 6) water-fed (H2O) and in wild type (n = 5) and YACtg152F7 transgenic (n = 7) green tea-fed (GTP). (Details of the MRI experiments in supp. data). ** for p<0.01; * for p<0.05.
Figure 4.
Effect of GTP treatment on short- and long-term memory.
In wild type (WT, n = 10) and YACtg152F7 transgenic (TG, n = 10) water-fed (H2O) and in wild type (WT, n = 10) and YACtg152F7 transgenic (TG, n = 10) green tea-fed (GTP, n = 10). A: Spontaneous alternation test with two sessions of ten minutes each separated by 24 h: number of alternations/total number of possible alternations ×100 (AS1). B: Object recognition test: difference in exploration time between the new and familiar objects, in percentage of total time spent exploring the two objects; 100×(N−F/N+F). ** for p<0.01, * for p<0.05. according to Wilcoxon test results (two-way ANOVA in supplementary data). C: Object recognition test on WT H2O-fed (n = 10), WT polyphenon-fed (n = 10) and TG polyphenon-fed (n = 6) (no significant differences between the three groups).
Figure 5.
Effect of GTP treatment on BDNF and TRKB mRNA levels.
mRNA levels determined by quantitative PCR. A: BDNF in fetal human hippocampus (EU: normal karyotype (n = 4) and T21: trisomy 21 (n = 5); B: BDNF in adult hippocampus from wild type (WT; n = 6), YACtg152F7 transgenic (TG; n = 10), water-fed (H2O) WT (n = 8), TG (n = 3), green tea-fed (GTP); C: TRKB in adult hippocampus from wild type (WT; n = 4), YACtg152F7 transgenic (TG; n = 18), water-fed (H2O) WT (n = 4), TG (n = 4) green tea-fed (GTP). ** for p<0.01; * for p<0.05.