Fig. 4: Increased membrane permeability in response to toxic insults in the neurons with inefficient endogenous γ-secretase.
From: A unique subpopulation of wild-type neurons recapitulating familial Alzheimer’s disease phenotypes
A Neurons expressing the C99 Y-T FRET biosensor were incubated with 100 μM Glu, 100 μM DTDP, or vehicle in the presence of 5 μg/mL propidium iodide (PI), and the time until becoming PI positive was measured on a cell-by-cell basis. Scale bar 100 μm. B Both Glu and DTDP significantly decreased the time until PI (+) compared to vehicle, but Individual neurons differently became PI positive. N = 49–57 neurons. One-way ANOVA, ****<0.0001. C Baseline γ-secretase activity was measured using the C99 720-670 biosensor and the neurons were divided into four groups based on γ-secretase activity (720/670 ratio: below -1 standard deviation (SD), −1SD to Mean, Mean to +1 SD, and over +1 SD), and the time until becoming PI (+) after treatment with vehicle (N = 6–31 neurons) (D), 100 μM Glu (N = 33–34 neurons) (E), or 100 μM DTDP (N = 23 neurons) (F) was compared among the groups. Scale bar 30 μm. One-way ANOVA, *<0.05, **<0.01, ***<0.001.
