Figure 1.
Triptolide treatment rescues spatial learning and memory deficits in APP/PS1 mice.
A, Escape latency during the acquisition phase of the Morris water maze test. Untreated control APP/PS1 mice exhibited learning deficits in locating the submerged escape platform, whereas triptolide-treated mice performed similarly to non-Tg mice. B, The number of crossings over the previously hidden platform area in the probe trial. Triptolide-treated group crossed the platform area significantly more often than control APP/PS1 group. C and D, Escape latency and swimming speed during the visible platform phase of the Morris water maze test. No significant differences were observed among different groups. For clarity, error bars are shown in only one direction. N = 7 mice/group; Age = 8 months; *, P<0.05.
Figure 2.
Triptolide treatment restores intersessional habituation in APP/PS1 mice.
A,Untreated control APP/PS1 mice were more active than mice in any other groups and did not show intersessional habituation. Triptolide-treated APP/PS1 mice, in contrast, performed similarly as non-Tg mice and displayed intersessional habituation shown by decreasing activity in the latter 2 days of testing. B, Triptolide treatment had no effect on anxiety levels in the elevated plus maze tests. N = 7 mice/group; Age = 8 months; *, P<0.05.
Figure 3.
Triptolide treatment reduces cerebral Aβ levels in APP/PS1 mice.
Carbonate-soluble (A) and carbonate-insoluble (guanidine-soluble) (B) Aβ40 and Aβ42 levels in cerebral homogenates were measured by ELISA. A, There was a trend for a reduced level of carbonate-soluble Aβ in triptolide-treated mice, but the difference did not reach statistical significance. B, Significant reductions in the levels of guanidine-soluble Aβ42 were observed in triptolide-treated mice. N = 7 mice/group; Age = 8.6 months; *, P<0.05.
Figure 4.
Triptolide treatment significantly decreases cerebral Aβ plaque load in APP/PS1 mice.
A, Representative brain sections of cortical and hippocampal areas from different groups immunostained with anti-Aβ antibody (6E10). B, C, Quantification of the percent amyloid load in the cortical (B) and hippocampal (C) areas, showing a significant reduction in the triptolide-treated group when compared to the control group. N = 7 mice/group; Age = 8.6 months; *, P<0.05. Scale bars = 100 µm.
Figure 5.
Triptolide treatment does not affect APP processing.
A, Immunoblot analysis of full-length APP (FL-APP), carboxyl-terminal fragments (CTFα and CTFβ), and amino-terminal fragment of APP (sAPPα and sAPPβ). B, Densitometric analysis of immunoblots (normalized by the amount of β-actin) with the levels in the control group set as 100%. There were no differences in the amount of FL-APP, the ratio of β-CTF to α-CTF, and the ratio of sAPPβ to sAPPα between triptolide treated and control APP/PS1 mice. N = 7 mice/group; Age = 8.6 months.
Figure 6.
Effect of triptolide treatment on proteins involved in clearance/degradation of Aβ in APP/PS1 mice.
A, Immunoblot analysis of ApoE, NEP, and IDE levels in the cerebral homogenates. B, Densitometric analysis of immunoblots (normalized by the amount of tubulin), with the levels in the non-Tg group set as 100%. The level of IDE was significantly decreased in control APP/PS1 mice but restored to the normal level in triptolide-treated APP/PS1 mice. N = 7 mice/group; Age = 8.6 months; *, P<0.05.
Figure 7.
Triptolide treatment attenuates neuroinflammation in APP/PS1 mice.
A, Representative photomicrographs of activated microglia stained with IBA1 antibody. B, Quantification of percent IBA1 immunoreactivity in the cortex of triptolide-treated and control mice. C, Immunoblot analysis of IBA1 and NOS2 levels in the cerebral homogenates. D, Densitometric analysis of IBA1 and NOS2 immunoblots (normalized by the amount of tubulin), with the levels in the non-Tg group set as 100%. The levels of IBA1 and NOS2 were elevated in control APP/PS1 mice but significantly attenuated in triptolide-treated APP/PS1 mice. N = 7 mice/group; Age = 8.6 months; *, P<0.05.