Description of mouse cohorts
| Cohort | Treatment groups | Age at start | Dosage | Dosing length | Figures |
|---|---|---|---|---|---|
| Cohort 1 | TIMP2, TIMP2-hIgG4 | 6.5 M | 250 μg/kg | Single | Figure 1A (PK) |
| Cohort 2 | TIMP2, Ala-TIMP2 | 2 M | 250 μg/kg | Single | Figure 6B (PK) |
| Cohort 3 | Vehicle, TIMP2, TIMP2-hIgG4 | 23 M | 250 μg/kg | 4 weeks | Figures 1C–H (behavior and endogenous protein), 2A–C,F,G (immediate early genes and neurogenesis), 3A–I (synapses and microglia); Tables 2, 3 (gene expression) |
| Cohort 4 | Vehicle, TIMP2, Ala-TIMP2 | 21.5 M | 250 μg/kg | 4 weeks | Figure 6A (behavior) |
| Cohort 5 | Vehicle, TIMP2, Ala-TIMP2 | 21.7 M | 250 μg/kg | 4 weeks | Figure 6C–E (synapses) |
| Cohort 6 | Vehicle, TIMP2 | 18 M | 50 μg/kg | 1 week | Figure 2D,E (iDISCO c-Fos); Movie 1 |
| Cohort 7 | Vehicle, TIMP2, TIMP2-hIgG4 | 22 M | 1 mg/kg | Single | Figure 3J (brain penetrance) |
Table provides details on each mouse cohort used and corresponding figures. M, months; PK, pharmacokinetics.