Effect of γ-secretase inhibition on the vulnerability of primary neurons to OGD. (A) Experimental design. Effect of γ-secretase inhibition on the vulnerability.

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Effect of γ-secretase inhibition on the vulnerability of primary neurons to OGD. (A) Experimental design. Effect of γ-secretase inhibition on the vulnerability of primary neurons to OGD. (A) Experimental design. Primary neurons isolated from Wt and Tg2576 mice were treated with LY450139 from 2 DIV to the end of the experiment. At 7 DIV, cells were exposed to 3 h of OGD and 24 h of reperfusion in the previous culture medium. (B) Representative images of 6E10 immunostaining of APPswe neurons, showing the intracellular accumulation of human APP protein/Aβ fragments. Scale bar: 50 µm. (C) Quantification of 6E10 in Tg2576 cells exposed to normoxia and treated or not with LY450139 (APPswe vehicle, n=5; APPswe LY450139, n=5). (D,E) Cell viability analysis of Wt and APPswe neurons exposed to normoxia and OGD, treated or not with LY450139, as established by mitochondrial function (E; Wt normoxia, n=10; Wt normoxia, LY450139, n=6; Wt OGD, n=10; Wt OGD LY450139, n=4; APPswe normoxia, n=7; APPswe normoxia LY450139, n=6; APPswe OGD, n=8; APPswe OGD LY450139, n=4) and nuclear morphology (F; Wt normoxia, n=6; Wt normoxia LY450139, n=4; Wt OGD, n=5; Wt OGD LY450139, n=4; APPswe normoxia, n=5; APPswe normoxia LY450139, n=4; APPswe OGD, n=5; APPswe OGD LY450139, n=5). Bars represent mean±s.e.m. Statistical analysis: one-way ANOVA followed by Tukey's multiple comparisons test inside the same genotype. Asterisks represent differences between LY450139- and vehicle-treated groups (*P<0.05; ***P<0.001; ****P<0.0001). Vito Antonio Baldassarro et al. Dis. Model. Mech. 2017;10:671-678 © 2017. Published by The Company of Biologists Ltd