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FKBP51 overexpression in the corticolimbic system stabilizes circadian rhythms
Niat T Gebru1, David Beaulieu-Abdelahad1, Danielle Gulick1
1Byrd Alzheimer's Center and Research Institute, Tampa, FL 33613, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA.
Cell Stress & Chaperones
|December 14, 2024
Summary
Elevated FKBP51 levels, linked to stress and PTSD, surprisingly improved circadian rhythms in mice. This suggests FKBP51 may protect against circadian disruption, especially in females.
Area of Science:
- Neuroscience
- Chronobiology
- Genetics
Background:
- Circadian rhythm disruptions are linked to health issues and sleep disorders.
- Post-traumatic stress disorder (PTSD) often involves circadian rhythm sleep disorders (CRSDs).
- FKBP51 gene variations influence PTSD susceptibility and FKBP51 levels after stress.
Purpose of the Study:
- To investigate the role of elevated FKBP51 in circadian rhythm disruption.
- To determine if FKBP51 overexpression impacts circadian rhythm regulation.
Main Methods:
- Utilized a transgenic mouse model (rTgFKBP5) overexpressing human FKBP51 in the forebrain.
- Compared circadian rhythm parameters between rTgFKBP5 mice and control groups.
- Measured corticosterone levels basally and after stress exposure.
Main Results:
- rTgFKBP5 mice exhibited greater circadian rhythm amplitude and less fragmentation.
- These beneficial effects on circadian rhythms were more pronounced in female mice.
- Female rTgFKBP5 mice displayed higher basal and stress-induced corticosterone levels.
Conclusions:
- FKBP51 overexpression is associated with enhanced circadian rhythm stability.
- Elevated FKBP51 may confer resilience against circadian rhythm disruption, particularly in females.
- This suggests a novel role for FKBP51 in regulating circadian rhythms.
