WT mice with short-term PERK inhibition are impaired in Y-maze spontaneous alternation.

<p>(A) Western blot analysis showing PERK inhibitor (PI) pretreatment prevented thapsigargin (TG)-induced phosphorylation of PERK and its substrate eIF2α in primary cortical neurons (one-way ANOVA followed by Bonferroni’s post-hoc test, * p<0.05, ** p<0.01). Cells were pretreated with 500 nM PI or DMSO for 15 min followed by co-treatment with or without 100 nM TG for 30 min. The phosphorylation level of PERK is shown by p-PERK blot, and the shifted band in PERK blot due to the dimerization and auto-phosphorylation of PERK after its activation. 3 replicates were included in the experiment and the quantification was performed on pooled results. (B) Schematic of PERK inhibitor treatment in spontaneous alternation Y-maze task. (C) Spontaneous alternation Y-maze task. Short-term PERK-inhibited mice showed a lower alteration rate compared to vehicle group (Vehicle n = 17, PERKi n = 18; ***p<0.001, two-tailed student’s t-Test). No difference was observed in the total number of arms entered (n.s. not significant, two-tailed student’s t-Test). Only male mice were used in the experiment.