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. 2022 Dec 7;42(49):9263–9277. doi: 10.1523/JNEUROSCI.0545-22.2022

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Figure 4. — Neuropathological analysis of striatal tissue of 12-month-old mice. A–C, HPLC analysis of olfactory bulb dopamine, DOPAC, and norepinephrine content normalized to total protein concentration. Olfactory bulb of right hemisphere of 12-month-old mice were used. Quantifications multiplied by factor of two to extrapolate to whole-brain values. Results are the mean ± SEM, n = 8–9 per group. Datasets were unbiasedly analyzed using ROUT outlier analysis with a maximum false discovery rate (q) of 0.1%. Data were found to be normally distributed via D'Agostino and Pearson test. SDs were not found to differ significantly. Significance of means was analyzed via an ordinary one-way ANOVA (A: F_(3,32) = 9.4 ***p = 0.0001; B: F_(3,32) = 2.4 ****p $<$ 0.00001; C: F_(3,32) = 5.886 **p = 0.0026). Post hoc Tukey's test resulted in A: **p = 0.046 for wild-type versus PolgA^D257A/D257A, ***p = 0.0002 for wild-type versus Parkin^–/–/PolgA^D257A/D257A, and *p = 0.0116 for Parkin^–/– versus Parkin^–/–/PolgA^D257A/D257A; B: *p = 0.0154 for wild-type versus Parkin^–/–, ****p $<$ 0.00001 for wild-type versus PolgA^D257A/D257A and for wild-type versus Parkin^–/–/PolgA^D257A/D257A, and *p = 0.0153 for Parkin^–/– versus Parkin^–/–/PolgA^D257A/D257A; C: **p = 0.0015 for wild-type versus Parkin^–/–/PolgA^D257A/D257A, ns, not significant. D, HPLC analysis of olfactory bulb HVA content normalized to total protein concentration. Olfactory bulb of right hemisphere of 12-month-old mice were used. Quantifications multiplied by factor of two to extrapolate to whole-brain values. Results are the mean ± SEM, n = 8–9 per group. Datasets were unbiasedly analyzed using ROUT outlier analysis with a maximum false discovery rate (q) of 0.1%. Data were found to be normally distributed via D'Agostino and Pearson test. SDs were found to differ significantly per Brown–Forsythe test of variance. Therefore, significance of means was analyzed via a Welch one-way ANOVA (D: W(3.0,16.71) = 28.77 ****p $<$ 0.00001). Post hoc Dunnett's T3 test resulted in ***p = 0.046 for wild-type versus PolgA^D257A/D257A, ****p $<$ 0.00001 for wild-type versus Parkin^–/–/PolgA^D257A/D257A, **p = 0.0031 for Parkin^–/– versus PolgA^D257A/D257A, and ***p = 0.0007 Parkin^–/– versus Parkin^–/–/PolgA^D257A/D257A, ns, not significant. E, F, HPLC analysis of olfactory bulb 5HT and 5HIAA content normalized to total protein concentration. Olfactory bulb of right hemisphere of 12-month-old mice were used. Quantifications multiplied by factor of two to extrapolate to whole-brain values. Results are the mean ± SEM, n = 8–9 per group. Datasets were unbiasedly analyzed using ROUT outlier analysis with a maximum false discovery rate (q) of 0.1%. Data were found to be normally distributed via D'Agostino and Pearson test. SDs were not found to differ significantly. Significance of means was analyzed via an ordinary one-way ANOVA (E: F_(3,32) = 7.249 ***p = 0.0008; F: F_(3,32) = 17.31 ****p $<$ 0.00001). Post hoc Tukey's test resulted in E: ***p = 0.004 for wild-type versus Parkin^–/–/PolgA^D257A/D257A; F: **p = 0.0056 for wild-type versus Parkin^–/–, ****p $<$ 0.00001 for wild-type versus PolgA^D257A/D257A and for wild-type versus Parkin^–/–/PolgA^D257A/D257A, ns, not significant. G, DOPAC-dependent dopamine turnover as assessed by (DOPAC+HVA)/dopamine. Significance of means analyzed via ordinary one-way ANOVA (F_(3,32) = 12.41 ****p $<$ 0.00001). Post hoc Tukey's test resulted in *p = 0.0260 for wild-type versus Parkin^–/–, ****p $<$ 0.00001 for wild-type versus PolgA^D257A/D257A and for wild-type versus Parkin^–/–/PolgA^D257A/D257A, ns, not significant. H, Serotonin (5HT) turnover as assessed by 5HIAA/5HT. Data were found to be normally distributed via D'Agostino and Pearson test. SDs were found to differ significantly per Brown–Forsythe test of variance. Therefore, significance of means was analyzed via a Welch one-way ANOVA (D: W(3.0,17.32) = 4.339 *p = 0.0142). Post hoc Dunnett's T3 test resulted in no significant differences (ns) between groups. Analysis and graphs were produced using GraphPad Prism 8.4.3.