1. PERK activator reduces behavioral deficits and neurodegeneration in vivo
PERK activator reduces behavioral deficits and neurodegeneration in vivo A–CYoung 9‐week‐old wild‐type (WT) and P301S tau transgenic mice were daily injected i.p. with 2 mg/kg PERK activator (PA) or normal saline (NS) for 6 weeks (n = 9 for WT groups; n = 8 for P301S groups). (A) Determination of spatial learning capacity by Morris water maze (MWM). The time required to find a hidden platform in a water basin after 3 training days was compared to day 1. (B) Representative photomicrographs of dendritic spines in the hippocampal CA1 area. Scale bar: 5 μm. (C) Quantification of dendritic spines (n = 3 per condition).D–FAged 17‐week‐old WT and P301S mice were daily injected i.p. with 2 mg/kg PA or NS for 6 weeks (n = 12 for PA‐treated P301S mice; n = 9 for all other groups). (D) Rotarod test was used to evaluate balancing abilities, measuring the time until mice fell off a rotating rod. (E) The number of adductor motoneurons of lamina 9 (Ad9) and quadriceps motoneurons of lamina 9 (Q9) were quantified in lumbar segments 2–3 of the spinal cord on five consecutive sections. (F) Representative photomicrographs of Ad9 and Q9. Arrows highlight examples of abnormally swollen or atrophic neurons. Scale bar: 100 μm.Data information: Data are mean + SEM. Statistical analysis in (A, C–E) was one‐way ANOVA with Tukey's or Fisher's LSD (E) post hoc test; *P < 0.05, ***P < 0.001 versus WT+NS; #P < 0.05, ##P < 0.01, ###P < 0.001, ns: not significant.
Julius Bruch et al. EMBO Mol Med. 2017;emmm
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