Fig. 9: S1P and YAPdeltaC rescue ER instability and cognitive impairment in AD model mice. | Nature Communications

Fig. 9: S1P and YAPdeltaC rescue ER instability and cognitive impairment in AD model mice.

From: YAP-dependent necrosis occurs in early stages of Alzheimer’s disease and regulates mouse model pathology

Fig. 9

a Experimental protocol for the rescue effect of S1P or YAPdeltaC (YAPdC) on ER instability and cell death in 5xFAD mice. Two protocols, administration before symptomatic onset (1 month) or administration just after onset (5 months), were used. AAV-NINS: AAV-CMV-no insert. b Alteration rate in Y-maze test of 6-month-old 5xFAD mice that had been treated with S1P from 1 month (upper left panel) or 5 months (lower left panel) or injected with AAV-YAPdeltaC at 1 month (upper right panel) or 5 months (lower right panel). P-values were determined by Tukey’s HSD test, *p < 0.05, **p < 0.01. N: shown below graphs. c ER instability was rescued at 6 months following treatment from 1 month with S1P or YAPdeltaC. P-values were determined by Welch’s test, **p < 0.01 (N = 3 mice, n = 9 cells). d Pathological examination at 6 months following treatment from 1 month with S1P or YAPdeltaC. Staining of YAP with the sc-15407 antibody detecting YAP-FL and YAPdeltaC, intracellular/extracellular Aβ, and pSer46MARCKS is shown. Right graphs show quantification of the four stains before and after the treatment. P-values were determined by Welch’s test, **p < 0.01 (N = 3 mice, n = 30 or 60). e Western blot with anti-Aβ antibody (82E1) confirmed the effect of S1P and AAV-YAPdC on Aβ burden in 5xFAD mice. f ELISA of Aβ1-40 and Aβ1–42 consistently showed the effect of S1P and AAV-YAPdC reducing Aβ burden in 5xFAD mice. P-values were determined by Tukey’s HSD test, *p < 0.05, **p < 0.01 (n = 4 mice). g Western blot confirming the increase of YAPdeltaC protein in cerebral cortex tissue of 5xFAD mice after AAV-YAPdeltaC infection. S1P also increased YAPdeltaC. P-values were determined by Tukey’s HSD test, #p < 0.05, ##p < 0.01 (n = 3 tests). h Immunohistochemistry of cerebral cortex tissue of 5xFAD mice supported the increase of total YAP after S1P and AAV-YAPdeltaC treatments. P-values were determined by Tukey’s HSD test, ##p < 0.01 (n = 50 cells). Box plots show the median, quartiles and whiskers that represent 1.5× the interquartile range. Bar graphs indicate average and mean S.E.M., together with the corresponding data points. Source data are provided as a “Source Data file”.

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