Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein

Park et al. 10.1073/pnas.0711568105.

Supporting Information

Files in this Data Supplement:

SI Figure 6
SI Figure 7
SI Figure 8
SI Figure 9
SI Table 1
SI Table 2
SI Table 3

Fig. 6. Nox2 inactivation rescues the cerebrovascular dysfunction in Tg2576 mice. CBF responses to topical neocortical application of A23187 (3 mM) (A), or hypercapnia (pCO2 = 50-60 mmHg) (B) in young and aged WT, Nox2^-/-, Tg2576, or Tg2576/Nox2^-/- mice. *, P < 0.05 from young WT; analysis of variance and Tukey's test; n = 5 per group.

Fig. 7. Oxidative stress in 12-15-month-old wild type and Tg2576 mice. (A) In wild type mice, the ROS signal (b and e) does not colocalize with GFAP-positive astrocytes (a and c) or with CD11b-positive microglia/macrophages (d and f). (B) In Tg2576 mice, there is activation of astrocytes (a) and microglia (j), but the ROS signal is not increased in these cells (b and k; see also merged panels c and l). (d, e, f, m, n, and o) Enlargements of the area in the white squares in a, b, c, j, k, and l, respectively. The ROS signal in astrocytes (g, h, and i) and microglia (p, q, and r) is increased by superfusion with the PKC activator PMA. (Scale bars: 20 mm.)

Fig. 8. Short-term application of ROS scavengers counteracts the cerebrovascular dysfunction in 12- to 15-month-old Tg2576 mice. MnTBAP, gp91ds-tat (gp91ds) or the scrambled peptide (sgp91ds) do not affect resting CBF (A and D) or the CBF response to hypercapnia (C and F). The cerebrovascular responses to A23187 is rescued by a 30 min neocortical application of MnTBAP (B) or gp91-ds (E) but not sgp91ds (E). *, P < 0.05 from vehicle; analysis of variance and Tukey's test; n = 5 per group.

SI Figure 9

Fig. 9. Amyloid angiopathy in Tg2576 mice. Thioflavine S-stained brain sections at the level of the somatosensory cortex in 12-month-old (A) and 16-month-old (B) Tg2576 mice. Vascular amyloid deposition was sparse at 12 months of age (arrow in A), but more abundant at 16 months (arrow in B). (Scale bar: 200 mm.)

Fig. 10. Brain Ab and amyloid burden are not reduced in 24-month-old Tg2576 mice lacking Nox2. SDS-soluble (A) and -insoluble (B) Ab are not different in Tg2576 and Tg2576/Nox2^-/- mice. The amyloid load is comparable between Tg2576 (C) and Tg2576/Nox2^-/- mice (D).

Table 1. Mean arterial pressure (MAP) and blood gases in young and aged Tg2576 mice

Mean ± SEM. Young, 3-4 months; aged, 12-15 months.

Table 2. Mean arterial pressure and blood gases in aged Tg2576 mice treated with MnTBAP

Table 3. Mean arterial pressure and blood gases in aged Tg2576 mice treated with gp91ds-tat

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