Fig. 3
From: Torpor induces reversible tau hyperphosphorylation and accumulation in mice expressing human tau
Cells with accumulated p-tau in mtau and htau brains (A, B) Representative total coronal slices and zoom-ins of the PPC, HIP, PIR and CoA for (A) mtau and (B) htau EU, T, A and 24 h post-torpor mice. Zoom-ins reveal diffuse AT8 staining in all torpor stages in mtau mice, whereas in htau mice EU, T, A and 24 h post-torpor mice show cells with p-tau accumulation in all four brain areas. Upper left corners show extra zoom-ins of the indicated areas. Below are zoom-ins of somato-dendritic accumulation of phosphorylated tau in hippocampus that are observed in htau mice specifically in all phases of daily torpor. Scale bars represent 200 and 20 μm. (C, D) The number of cells with p-tau accumulation per brain area (the same size of the brain area was measured for every animal; 5.6 × 107 for total slice, 3.5 × 106 for HIP and 7,0 × 105 for PPC, PIR and CoA) was determined in EU, A and 24 h post-torpor (note that cells with p-tau accumulation could not be measured during torpor due to high AT8 intensities) for PPC, HIP, PIR and CoA of (C) mtau mice and (D) htau mice. Cells with p-tau accumulation were low in mtau mice and not significantly higher during arousal (EU vs. A, p > 0.05 for all, total slice: F2, 14 = 2.179, HIP F2, 13 = 1.845, PPC F2, 15 = 1.503, PIR: F2, 13 = 1.472 and CoA: F2, 13 = 1.0771-Way ANOVA). In htau mice on the other hand, cells with p-tau accumulation already appeared in EU and were significantly higher during arousal for total slice, HIP, PIR and CoA (EU vs. A; p < 0.05, total slice: t = 2.595, df = 11, HIP: t = 2.777, df = 11, PPC: t = 2.008, df = 11, PIR: t = 2.315, df = 10 and CoA: t = 2.673, df = 9; 1-Way ANOVA, for all areas). 24 h after torpor the number of cells with p-tau accumulation reversed back to euthermic levels (p > 0.05; 1-Way ANOVA; total slice: t = 0.1651, df = 11; HIP: t = 0.2326, df = 11; PPC: t = 0.2995, df = 11; PIR: t = 0.3026, df = 10; and CoA: df = 9, t = 0.2326). Though not significant, levels of cells with p-tau accumulation appeared lower at 24 h vs. A in htau mice (total slice: 2588 ± 2030 vs. 1922 ± 710.1, HIP: 139.3 ± 65.4 vs. 49.5 ± 16.2, PPC: 223.3 ± 103.9 vs. 71.4 ± 57.4, PIR: 240.4 ± 137.4 vs.89.4 ± 51.2 and CoA: 172.3 ± 114.4 vs. 49.8 ±. 24.4). *p < 0.05