Table 1.
Respiration of intrasynaptosomal mitochondria in transgenic mouse models with AD-like phenotypes
| A. J20 mice | Age 6 months |
|||
|---|---|---|---|---|
| Cortex |
Hippocampus |
|||
| Wild type (n = 5) | Transgenic (n = 5) | Wild type (n = 5) | Transgenic (n = 5) | |
| Non-mitochondrial respiration (pmol O2/min/10 μg protein) | 52.1 ± 5.7 | 67.3 ± 10.5# | 55.4 ± 8.2 | 62.1 ± 4.2 |
| Basal respiration (pmol O2/min/10 μg protein) | 150 ± 5.0 | 148 ± 6.6# | 149 ± 9.3 | 151 ± 11.3# |
| Respiration driving ATP synthesis (pmol O2/min/10 μg protein) | 51.9 ± 3.7 | 54.6 ± 2.9# | 67.5 ± 5.1 | 57.5 ± 3.7 |
| Respiration driving proton leak (pmol O2/min/10 μg protein) | 74.2 ± 1.9 | 87.8 ± 5.6## | 68.5 ± 3.6 | 77.0 ± 4.7## |
| Maximum respiration (pmol O2/min/10 μg protein) | 959 ± 71 | 1150 ± 54## | 1142 ± 82 | 1227 ± 70# |
| Cell respiratory control (%) | 1289 ± 67 | 1329 ± 107# | 1728 ± 170 | 1665 ± 75 |
| Coupling efficiency (%) | 40.8 ± 2.1 | 38.4 ± 1.3# | 49.6 ± 1.6 | 45.7 ± 1.2# |
| Spare respiratory capacity (%) | 765 ± 62 | 812 ± 48# | 860 ± 70 | 921 ± 34# |
| B. Tg2576 mice | Age 16 months |
|
|---|---|---|
| Cortex | ||
| Wild type (n = 6) | Transgenic (n = 6) | |
| Non-mitochondrial respiration (pmol O2/min/10 μg protein) | 91.0 ± 13 | 80.0 ± 9.5 |
| Basal respiration (pmol O2/min/10 μg protein) | 180 ± 28 | 151 ± 27 |
| Respiration driving ATP synthesis (pmol O2/min/10 μg protein) | 65.3 ± 8.0 | 63 ± 14 |
| Respiration driving proton leak (pmol O2/min/10 μg protein) | 114 ± 21 | 90 ± 26 |
| Maximum respiration (pmol O2/min/10 μg protein) | 547 ± 119 | 413 ± 85 |
| Cell respiratory control (%) | 311 ± 17 | 315 ± 29# |
| Coupling efficiency (%) | 36.1 ± 4.8 | 46.3 ± 13.0 |
| Spare respiratory capacity (%) | 280 ± 23 | 276 ± 21 |
| C. APP/PS mice | Age 9 months |
Age 14 months |
||||
|---|---|---|---|---|---|---|
| Cortex |
Cortex |
hippocampus |
||||
| Wild type (n = 4) | Transgenic (n = 4) | Wild type (n = 3) | Transgenic (n = 6) | Wild type (n = 3) | Transgenic (n = 4) | |
| Basal respiration (pmol O2/min/10 μg protein) | 138 ± 8.6 | 159 ± 13## | 104 ± 12 | 170 ± 17*## | 131 ± 34 | 128 ± 10.8 |
| Genotype* | ||||||
| Respiration driving ATP synthesis (pmol O2/min/10 μg protein) | 59.5 ± 3.8 | 71.2 ± 7.9# | 60.4 ± 9.0 | 72.4 ± 6.2# | 71 ± 13.6 | 67 ± 6.6 |
| Respiration driving proton leak (pmol O2/min/10 μg protein) | 71.4 ± 4.7 | 89.5 ± 5.1*## | 43.3 ± 5.5 | 97.5 ± 11.3** | 60 ± 21 | 60 ± 6.6 |
| Genotype** | ||||||
| Maximum respiration (pmol O2/min/10 μg protein) | 1010 ± 82 | 1096 ± 77# | 495 ± 67 | 659 ± 72## | 448 ± 86.5 | 539 ± 54 |
| Age*** | ||||||
| Cell respiratory control (%) | 1418 ± 92 | 1225 ± 33 | 1165 ± 63 | 712 ± 28** | 864 ± 166 | 902 ± 72 |
| Age*** and Genotype***, interacting* | ||||||
| Coupling efficiency (%) | 47.9 ± 3.2 | 43.1 ± 1.7 | 57.0 ± 3.8 | 42.5 ± 1.6* | 57 ± 6.6 | 54 ± 2.5 |
| Genotype** | ||||||
| Spare respiratory capacity (%) | 1024 ± 101 | 1080 ± 96 | 489 ± 27 | 402 ± 20 | 358 ± 65 | 420 ± 26 |
| Age*** | ||||||
Three transgenic mice models with known disease phenotypes, J20 (A), Tg2576 (B), and APP/PS (C), were chosen and the respiration rates of synaptosomes were compared with those of age-matched controls. *p < 0.05; **p < 0.01 significance by two-tailed Welch t test. For nonsignificant differences,
#>20%;
##>10% decrease compared to wild type can be excluded at p = 0.05 (one-tailed confidence interval). In C, non-mitochondrial respiration was not measured, but was taken as 44% of uncorrected rate in the presence of oligomycin, based on A and B. In C, effects of age and the genotype were investigated by two-way ANOVA performed independently for each variable for cortical synaptosomes.
*p < 0.05;
**p < 0.01;
***p < 0.001 mark significance for the indicated category (Age or Genotype).