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. Author manuscript; available in PMC: 2021 Aug 2.
Published in final edited form as: Sci Signal. 2021 Feb 2;14(668):eabc5429. doi: 10.1126/scisignal.abc5429

Figure 2. Systemic treatment with ISRIB prevents memory impairment induced by eIF2α-P.

Figure 2.

(A) ISRIB concentrations in plasma and brain were determined by mass spectrometry 4 or 24 hours after i.p. administration (0.25 mg/kg for 6 consecutive days) in mice (N = 4 mice/time point). (B) Experimental timeline: C57BL/6 mice were treated with salubrinal alone (10 mg/kg, i.p.; orange arrows) or salubrinal + ISRIB (0.25 mg/kg, i.p.; black arrows) on days 1–5, 7, 9–11. Mice were trained and tested in the Novel Object Recognition (NOR) task on days 6 and 7, respectively, and were trained and tested in the Contextual Fear Conditioning (CFC) task on days 8 and 9, respectively. Brains were collected on day 12. (C) Discrimination index in the NOR test (F = 12.00; N = 5–7 mice/group;). (D) Freezing time in the CFC test (F = 5.049; N = 5–7 mice/group). (E) Hippocampal eIF2α-P in mice treated with salubrinal alone or salubrinal + ISRIB, normalized by total eIF2α (N = 6–7 mice/group; F = 5.461). In all panels, dots correspond to individual mice. *p < 0.05, **p < 0.01, ***p<0.001, One-way ANOVA followed by Dunnet’s post hoc test.