FKBP51 overexpression in the corticolimbic system stabilizes circadian rhythms

Circadian rhythm disruptions have been associated with a wide range of health issues and complications, including an increased risk of circadian rhythm sleep disorders (CRSDs). CRSDs are common among individuals who have been through a traumatic event, particularly in those who have post-traumatic stress disorder (PTSD). Allelic variations in the gene encoding for FK506-binding protein 51 (FKBP51) can increase the susceptibility for PTSD and other stress-related disorders following trauma. At least one of these variants increases the levels of FKBP51 following stress through a glucocorticoid receptor-mediated process. Here, we used a mouse model that overexpresses human FKBP51 throughout the forebrain, rTgFKBP5, to investigate if elevated FKBP51 contributes to circadian rhythm disruption. Surprisingly, our findings indicate a greater rhythm amplitude and decreased rhythm fragmentation in rTgFKBP5 mice, particularly females, compared to controls. Female rTgFKBP5 mice also showed higher corticosterone levels basally and following stress exposure. Overall, this study associates FKBP51 overexpression with beneficial circadian rhythm outcomes.