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Deficiency of FK506-binding protein (FKBP) 51 alters sleep architecture and recovery sleep responses to stress in mice.
J Sleep Res. 2014 Apr; 23(2):176-85.JS

Abstract

FK506-binding protein 51 (FKBP51) is a co-chaperone of the glucocorticoid receptor, functionally linked to its activity via an ultra-short negative feedback loop. Thus, FKBP51 plays an important regulatory role in the hypothalamic-pituitary-adrenocortical (HPA) axis necessary for stress adaptation and recovery. Previous investigations illustrated that HPA functionality is influenced by polymorphisms in the gene encoding FKBP51, which are associated with both increased protein levels and depressive episodes. Because FKBP51 is a key molecule in stress responses, we hypothesized that its deletion impacts sleep. To study FKBP51-involved changes in sleep, polysomnograms of FKBP51 knockout (KO) mice and wild-type (WT) littermates were compared at baseline and in the recovery phase after 6-h sleep deprivation (SD) and 1-h restraint stress (RS). Using another set of animals, the 24-h profiles of hippocampal free corticosterone levels were also determined. The most dominant effect of FKBP51 deletion appeared as increased nocturnal wake, where the bout length was significantly extended while non-rapid eye movement sleep (NREMS) and rapid eye movement sleep were rather suppressed. After both SD and RS, FKBP51KO mice exhibited less recovery or rebound sleep than WTs, although slow-wave activity during NREMS was higher in KOs, particularly after SD. Sleep compositions of KOs were nearly opposite to sleep profiles observed in human depression. This might result from lower levels of free corticosterone in FKBP51KO mice, confirming reduced HPA reactivity. The results indicate that an FKBP51 deletion yields a pro-resilience sleep phenotype. FKBP51 could therefore be a therapeutic target for stress-induced mood and sleep disorders.

Authors+Show Affiliations

Max Planck Institute of Psychiatry, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

24354785

Citation

Albu, Stefana, et al. "Deficiency of FK506-binding Protein (FKBP) 51 Alters Sleep Architecture and Recovery Sleep Responses to Stress in Mice." Journal of Sleep Research, vol. 23, no. 2, 2014, pp. 176-85.
Albu S, Romanowski CP, Letizia Curzi M, et al. Deficiency of FK506-binding protein (FKBP) 51 alters sleep architecture and recovery sleep responses to stress in mice. J Sleep Res. 2014;23(2):176-85.
Albu, S., Romanowski, C. P., Letizia Curzi, M., Jakubcakova, V., Flachskamm, C., Gassen, N. C., Hartmann, J., Schmidt, M. V., Schmidt, U., Rein, T., Holsboer, F., Hausch, F., Paez-Pereda, M., & Kimura, M. (2014). Deficiency of FK506-binding protein (FKBP) 51 alters sleep architecture and recovery sleep responses to stress in mice. Journal of Sleep Research, 23(2), 176-85. https://doi.org/10.1111/jsr.12112
Albu S, et al. Deficiency of FK506-binding Protein (FKBP) 51 Alters Sleep Architecture and Recovery Sleep Responses to Stress in Mice. J Sleep Res. 2014;23(2):176-85. PubMed PMID: 24354785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deficiency of FK506-binding protein (FKBP) 51 alters sleep architecture and recovery sleep responses to stress in mice. AU - Albu,Stefana, AU - Romanowski,Christoph P N, AU - Letizia Curzi,M, AU - Jakubcakova,Vladimira, AU - Flachskamm,Cornelia, AU - Gassen,Nils C, AU - Hartmann,Jakob, AU - Schmidt,Mathias V, AU - Schmidt,Ulrike, AU - Rein,Theo, AU - Holsboer,Florian, AU - Hausch,Felix, AU - Paez-Pereda,Marcelo, AU - Kimura,Mayumi, Y1 - 2013/12/05/ PY - 2013/05/14/received PY - 2013/10/22/accepted PY - 2013/12/21/entrez PY - 2013/12/21/pubmed PY - 2014/6/10/medline KW - FKBP51 KW - depression KW - free corticosterone KW - rapid eye movement sleep KW - restraint stress KW - slow-wave activity SP - 176 EP - 85 JF - Journal of sleep research JO - J Sleep Res VL - 23 IS - 2 N2 - FK506-binding protein 51 (FKBP51) is a co-chaperone of the glucocorticoid receptor, functionally linked to its activity via an ultra-short negative feedback loop. Thus, FKBP51 plays an important regulatory role in the hypothalamic-pituitary-adrenocortical (HPA) axis necessary for stress adaptation and recovery. Previous investigations illustrated that HPA functionality is influenced by polymorphisms in the gene encoding FKBP51, which are associated with both increased protein levels and depressive episodes. Because FKBP51 is a key molecule in stress responses, we hypothesized that its deletion impacts sleep. To study FKBP51-involved changes in sleep, polysomnograms of FKBP51 knockout (KO) mice and wild-type (WT) littermates were compared at baseline and in the recovery phase after 6-h sleep deprivation (SD) and 1-h restraint stress (RS). Using another set of animals, the 24-h profiles of hippocampal free corticosterone levels were also determined. The most dominant effect of FKBP51 deletion appeared as increased nocturnal wake, where the bout length was significantly extended while non-rapid eye movement sleep (NREMS) and rapid eye movement sleep were rather suppressed. After both SD and RS, FKBP51KO mice exhibited less recovery or rebound sleep than WTs, although slow-wave activity during NREMS was higher in KOs, particularly after SD. Sleep compositions of KOs were nearly opposite to sleep profiles observed in human depression. This might result from lower levels of free corticosterone in FKBP51KO mice, confirming reduced HPA reactivity. The results indicate that an FKBP51 deletion yields a pro-resilience sleep phenotype. FKBP51 could therefore be a therapeutic target for stress-induced mood and sleep disorders. SN - 1365-2869 UR - https://www.unboundmedicine.com/medline/citation/24354785/Deficiency_of_FK506_binding_protein__FKBP__51_alters_sleep_architecture_and_recovery_sleep_responses_to_stress_in_mice_ L2 - https://doi.org/10.1111/jsr.12112 DB - PRIME DP - Unbound Medicine ER -