Figure 5.

Genetic Modulation of Astrocytic PERK-eIF2α Signaling Ameliorates the UPR-Reactivity State In Vivo

(A) Prion-inoculated mice were injected with lentivirus at 5 w.p.i., prior to synapse loss. The astrocytic expression of ΔhuGADD34 significantly reduced the mRNA levels of the UPR-reactivity markers C3 and Lcn2 at 10 w.p.i., as analyzed by qPCR. ^∗∗p < 0.01; n = 5 mice per condition.

(B) RNA scope also revealed a reduction in C3 and Lcn2 upon the expression of ΔhuGADD34.

(C and D) Protein levels of C3 (C) and LCN2 (D) were similarly reduced by astrocytic ΔhuGADD34, as determined by immunohistochemistry. Scale bars, 100 μm.

(E) Bar graphs represent quantification of C3⁺ and LCN2⁺ astrocytes treated with ΔhuGADD34 or empty virus. Bar graphs show mean ± SEM; ^∗∗∗p < 0.001; Student’s t test. n = 3 mice.