In:
Journal of Sleep Research, Wiley, Vol. 23, No. 2 ( 2014-04), p. 176-185
Abstract:
FK 506‐binding protein 51 ( FKBP 51) is a co‐chaperone of the glucocorticoid receptor, functionally linked to its activity via an ultra‐short negative feedback loop. Thus, FKBP 51 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 FKBP 51, which are associated with both increased protein levels and depressive episodes. Because FKBP 51 is a key molecule in stress responses, we hypothesized that its deletion impacts sleep. To study FKBP 51‐involved changes in sleep, polysomnograms of FKBP 51 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 FKBP 51 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 , FKBP 51 KO mice exhibited less recovery or rebound sleep than WT s, although slow‐wave activity during NREMS was higher in KO s, particularly after SD . Sleep compositions of KO s were nearly opposite to sleep profiles observed in human depression. This might result from lower levels of free corticosterone in FKBP 51 KO mice, confirming reduced HPA reactivity. The results indicate that an FKBP 51 deletion yields a pro‐resilience sleep phenotype. FKBP 51 could therefore be a therapeutic target for stress‐induced mood and sleep disorders.
Type of Medium:
Online Resource
ISSN:
0962-1105
,
1365-2869
DOI:
10.1111/jsr.2014.23.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2007459-1
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