Figure 1.

One i.p. injection with 10 mg/kg GBZ reduces ATF4 transcriptome in WT and 2b5 ^ho mice. Four‐month‐old male WT (open symbols) and early symptomatic 2b5 ^ho mice (closed symbols) received one i.p. injection of saline (placebo, black) or 10 mg/kg GBZ (blue). Mice were terminated 4 or 24 h after injection. Brains were taken out and sagittally cut. One half was lysed to obtain protein samples and total RNA samples as described. ¹⁵ , ²⁹ Western blot and qPCR were performed for indicated ISR markers (Akt was used as reference in qPCR). ¹³ A simplified overview of the ISR pathway is shown; Ddit3/Chop, Trib3, and Gadd34 are part of the ATF4‐regulated transcriptome. GADD34 is part of the negative feedback loop and dephosphorylates eIF2 when bound to protein phosphatase 1c. Graphs show individual and mean values, ±SD. qPCR and Western blot samples were derived from the same mouse. n = 2 animals per treatment group. Statistically significant differences between placebo‐treated WT and placebo‐treated 2b5 ^ho mice are not indicated. Treatment effects on protein levels were statistically analyzed with an unpaired t‐test. *p < 0.05, **p < 0.01. [Colour figure can be viewed at wileyonlinelibrary.com]