Association of FKBP51 with Priming of Autophagy Pathways and Mediation of Antidepressant Treatment Response: Evidence in Cells, Mice, and Humans
Figure 4
Deletion of FKBP51 diminishes the physiological effects of chronic stress and chronic PAR treatment.
(A) Time course of the experiment. Body weight was assessed on day 1, day 22, and day 43. Basal corticosterone was measured on day 22 and day 43. The behavioral testing (open-field test, social avoidance test, and FST) and the stress response test (corticosterone samples 30 min and 90 after the FST) were performed in the last week of the treatment phase. (B–G) Weights of body, thymus, and adrenal glands. When the three-way ANOVA indicated an interaction effect (p<0.1), genotype-dependent stress and treatment effects were isolated by normalizing the data to either unstressed controls or vehicle treatment. (B) Body weight was significantly reduced in 51KO mice before the start of the first defeat. At day 22, significant main effects for condition and genotype were observed: CSDS induced an increase of body weight in both wild-type and 51KO mice, while 51KO mice still showed reduced body weight compared to wild-type mice. (C and D) Stress-induced body weight increase was still present after 3 wk of recovery. PAR-induced increase of body weight was most pronounced under control conditions. 51KO mice were less affected by PAR-induced body weight increase. (E and F) 51KO mice showed overall reduced adrenal gland weight compared to wild-type mice. Adrenal gland weight was significantly increased in stressed animals. The stress effect was less pronounced in 51KO mice than in wild-type animals. PAR led to adrenal gland enlargement in wild-type mice and reduction in 51KO mice. (G) Thymus size was significantly reduced following CSDS. 51KO mice demonstrated significantly lower thymus weight than wild-type mice. Asterisks indicate significant result for planned contrast test for main genotype effect (#), main treatment effect ($), or main condition effect (+): *p<0.05; **p<0.01; ***p<0.001. See Table S1 for all statistical parameters. BW, body weight; WT, wild type.