Figure 5. Wfs1/CKO mice display hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis in response to stress.
Acute exposure to restraint stress significantly elevates cFos activation in the hypothalamic paraventricular nucleus in both groups of animals compared to basal conditions, but ARS also leads to a significantly higher increase of cFOS immunostaining in the PVN of Wfs1/CKO mice compared with controls (A and B) (Two-way ANOVA—Bonferroni post hoc test: WT + ARS vs CKO + ARS, p < 0.001***, N = 3 per group). Further downstream in the HPA axis, Wfs1/CKO mice release a significantly higher level of serum corticosterone (p < 0.001***) compared with controls (C) up on exposure to ARS (Two-way ANOVA—Bonferroni post hoc test: WT + ARS vs CKO + ARS, p < 0.001***, N = 5 per group). The intra-assay and inter-assay variability for the RIA were 5.08% CV and 1.99% CV, respectively. Our data support a model in which loss of Wfs1 in forebrain neurons causes hyperactivation of the PVN and the HPA axis is response to stress (D).