TABLE 1.
Quantitative results and statistical analyses of 8-oxo-dG and DHE staining intensities are shown as mean ± standard deviations in all investigated brain regions.
| 8-oxo-dG | 1 month | 3 months | 6 months | |||||||||||
| WT | KO | WT | KO | WT | KO | WT | ||||||||
| Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | Effect of age | → | p-value | Effect of genotype | → | p-value | R2–value | ||
| DG | 10.17 ± 1.36 | 10.51 ± 1.46 | 10.60 ± 0.97 | 10.77 ± 0.97 | 10.85 ± 0.88 | 11.11 ± 0.85 | F(2,24) = 0.8305 | 0.4480 | F(1,24) = 0.3980 | 0.5341 | 0.9306 | |||
| CA3 | 12.04 ± 0.93 | 12.23 ± 1.21 | 12.91 ± 0.81 | 12.91 ± 0.88 | 13.40 ± 0.65 | 13.98 ± 0.41 | F(2,24) = 8.3030 | 0.0018 | F(1,24) = 0.6919 | 0.4137 | 0.9263 | |||
| CA1 | 10.60 ± 1.27 | 11.47 ± 1.44 | 11.55 ± 0.71 | 11.81 ± 0.89 | 12.59 ± 0.56 | 12.67 ± 1.03 | F(2,24) = 6.0060 | 0.0077 | F(1,24) = 1.1330 | 0.2977 | 0.9921 | |||
| Striatum | 14.46 ± 0.97 | 15.36 ± 1.71 | 17.41 ± 1.81 | 20.89 ± 1.71 | 20.54 ± 1.75 | 21.88 ± 1.33 | F(2,24) = 41.2000 | <0.0001 | F(1,24) = 10.8800 | 0.0030 | 0.9905 | |||
| SSC | 15.35 ± 2.32 | 16.41 ± 1.27 | 17.06 ± 1.53 | 20.82 ± 2.25 | 22.20 ± 1.18 | 23.67 ± 2.08 | F(2,24) = 34.0800 | <0.0001 | F(1,24) = 8.94900 | 0.0063 | 0.9725 | |||
| mPFC | 20.09 ± 1.45 | 20.87 ± 1.87 | 24.24 ± 3.09 | 30.82 ± 3.60 | 25.37 ± 3.10 | 32.99 ± 3.54 | F(2,24) = 25.4600 | <0.0001 | F(1,24) = 22.2800 | <0.0001 | 0.8232 | |||
| PC | 21.05 ± 2.47 | 22.62 ± 1.61 | 30.99 ± 4.88 | 41.22 ± 2.82 | 44.01 ± 4.53 | 49.48 ± 2.24 | F(2,24) = 141.600 | <0.0001 | F(1,24) = 22.5200 | <0.0001 | 0.9986 | |||
| MLI | 20.68 ± 2.97 | 21.70 ± 1.95 | 29.66 ± 3.22 | 39.66 ± 2.35 | 42.03 ± 2.84 | 47.46 ± 2.68 | F(2,24) = 191.000 | <0.0001 | F(1,24) = 30.8000 | <0.0001 | 0.9994 | |||
| TRN | 33.33 ± 3.07 | 34.79 ± 1.74 | 37.08 ± 3.09 | 50.42 ± 3.17 | 44.58 ± 4.25 | 53.96 ± 2.37 | F(2,24) = 63.8900 | <0.0001 | F(1,24) = 52.4600 | <0.0001 | 0.9944 | |||
| 1 month | 3 months | 6 months | PV conc. | Mito. volume | ||||||||||
| WT vs. KO | WT vs. KO | WT vs. KO | in WT neurons | increase 3 m | ||||||||||
| p-value | p-value | p-value | ||||||||||||
| DG | 0.9962 | 0.9999 | 0.9990 | 20 μM | 11.3 | |||||||||
| CA3 | 0.9991 | >0.9999 | 0.8843 | 20 μM | 10.6 | |||||||||
| CA1 | 0.7731 | 0.9986 | >0.9999 | 20 μM | 13.4 | |||||||||
| Striatum | 0.9446 | 0.0210* | 0.7610 | 70 μM | 109.2 | |||||||||
| SSC | 0.9489 | 0.0496* | 0.8271 | 90 μM | 117.4 | |||||||||
| mPFC | 0.9980 | 0.0163* | 0.0042** | 120 μM | 130.8 | |||||||||
| PC | 0.9736 | 0.0007*** | 0.1356 | 100 μM | 58.2 | |||||||||
| MLI | 0.9904 | <0.0001**** | 0.0421* | 570 μM | 103.9 | |||||||||
| TRN | 0.9721 | <0.0001**** | <0.0007*** | 750 μM | 161.1 | |||||||||
| DHE | 1 month | 3 months | 6 months | |||||||||||
| WT | KO | WT | KO | WT | KO | WT | ||||||||
| Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | Effect of age | → | p-value | Effect of genotype | → | p-value | R2 value | ||
| DG | 5.73 ± 2.50 | 6.154 ± 1.82 | 6.068 ± 2.14 | 6.75 ± 1.33 | 6.67 ± 1.87 | 7.01 ± 1.92 | F(2,24) = 0.5208 | 0.6006 | F(1,24) = 0.4548 | 0.5065 | 0.9983 | |||
| CA3 | 6.80 ± 1.64 | 7.670 ± 1.43 | 8.155 ± 1.15 | 7.67 ± 2.33 | 8.93 ± 1.48 | 8.93 ± 2.44 | F(2,24) = 2.2250 | 0.1299 | F(1,24) = 0.0382 | 0.8466 | 0.9283 | |||
| CA1 | 5.86 ± 2.08 | 6.466 ± 1.52 | 6.552 ± 1.86 | 6.64 ± 2.18 | 7.33 ± 1.69 | 7.41 ± 2.00 | F(2,24) = 1.0280 | 0.3729 | F(1,24) = 0.1379 | 0.7137 | 0.9934 | |||
| Striatum | 8.43 ± 1.22 | 9.29 ± 0.96 | 9.375 ± 1.51 | 12.23 ± 0.81 | 10.18 ± 0.71 | 12.23 ± 1.50 | F(2,24) = 10.5300 | 0.0005 | F(1,24) = 18.6200 | 0.0002 | 0.9745 | |||
| SSC | 9.31 ± 1.45 | 9.71 ± 1.16 | 10.29 ± 1.05 | 12.57 ± 1.05 | 12.73 ± 1.01 | 14.04 ± 1.21 | F(2,24) = 27.4600 | <0.0001 | F(1,24) = 9.7400 | 0.0046 | 0.9843 | |||
| mPFC | 11.08 ± 0.89 | 11.69 ± 1.01 | 13.33 ± 0.77 | 15.06 ± 0.83 | 14.89 ± 0.51 | 15.93 ± 0.83 | F(2,24) = 61.5200 | <0.0001 | F(1,24) = 13.7000 | 0.0011 | 0.9527 | |||
| PC | 12.62 ± 1.11 | 12.67 ± 0.88 | 14.71 ± 0.97 | 18.14 ± 1.06 | 16.22 ± 1.03 | 17.91 ± 1.22 | F(2,24) = 51.1200 | <0.0001 | F(1,24) = 20.0000 | 0.0002 | 0.9575 | |||
| MLI | 18.81 ± 2.89 | 20.00 ± 1.75 | 19.49 ± 3.97 | 27.80 ± 2.57 | 22.54 ± 1.75 | 29.83 ± 3.51 | F(2,24) = 14.2600 | <0.0001 | F(1,24) = 28.5300 | <0.0001 | 0.9450 | |||
| TRN | 17.08 ± 2.50 | 20.21 ± 2.28 | 22.08 ± 4.25 | 32.08 ± 3.63 | 24.17 ± 3.85 | 34.38 ± 4.71 | F(2,24) = 23.6200 | <0.0001 | F(1,24) = 34.0400 | <0.0001 | 0.8839 | |||
| 1 month | 3 months | 6 months | PV conc. | Mito. volume | ||||||||||
| WT vs. KO | WT vs. KO | WT vs. KO | in WT neurons | increase 3 m | ||||||||||
| p-value | p-value | p-value | ||||||||||||
| DG | 0.9993 | 0.9993 | 0.9998 | 20 μM | 11.3 | |||||||||
| CA3 | 0.9713 | 0.9980 | >0.9999 | 20 μM | 10.6 | |||||||||
| CA1 | 0.9957 | >0.9999 | >0.9999 | 20 μM | 13.4 | |||||||||
| Striatum | 0.8955 | 0.0116* | 0.1152 | 70 μM | 109.2 | |||||||||
| SSC | 0.9932 | 0.0503 | 0.5052 | 90 μM | 117.4 | |||||||||
| mPFC | 0.8550 | 0.0325* | 0.3858 | 120 μM | 130.8 | |||||||||
| PC | >0.9999 | 0.0004*** | 0.1566 | 100 μM | 58.2 | |||||||||
| MLI | 0.9853 | 0.0015** | 0.0059** | 570 μM | 103.9 | |||||||||
| TRN | 0.7530 | 0.0028** | 0.0022** | 750 μM | 161.1 | |||||||||
Two-way ANOVA was performed for each brain region (upper parts) followed by Tukey’s multiple comparison (lower parts) for 8-oxo-dG and DHE signals. In addition, values of estimated PV concentrations in 3–5 months-old WT mice and mitochondria volume increase between 3-months old WT and KO mice are shown. The mean 8-oxo-dG and ox-DHE signal intensities were compared among groups using multivariate ANOVA followed by Tukey test for multiple comparisons. P-values > 0.05: not significant; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. From WT 8-oxo-dG and ox-DHE data (1, 3, and 6 months), linear regression analysis was performed and R2 values are listed.