Expression and Regulation of the Fkbp5 Gene in the Adult Mouse Brain

Research Group Molecular Stress Physiology, Max Planck Institute of Psychiatry, Munich, Germany.
PLoS ONE (Impact Factor: 3.23). 02/2011; 6(2):e16883. DOI: 10.1371/journal.pone.0016883
Source: PubMed


Chronic stress has been found to be a major risk factor for various human pathologies. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which is tightly regulated via, among others, the glucocorticoid receptor (GR). The activity of the GR is modulated by a variety of proteins, including the co-chaperone FK506 binding protein 51 (FKBP5). Although FKBP5 has been associated with risk for affective disorders and has been implicated in GR sensitivity, previous studies focused mainly on peripheral blood, while information about basal distribution and induction in the central nervous system are sparse.
In the present study, we describe the basal expression pattern of Fkbp5 mRNA in the brain of adult male mice and show the induction of Fkbp5 mRNA via dexamethasone treatment or different stress paradigms. We could show that Fkbp5 is often, but not exclusively, expressed in regions also known for GR expression, for example the hippocampus. Furthermore, we were able to induce Fkbp5 expression via dexamethasone in the CA1 and DG subregions of the hippocampus, the paraventricular nucleus (PVN) and the central amygdala (CeA). Increase of Fkbp5 mRNA was also found after restrained stress and 24 hours of food deprivation in the PVN and the CeA, while in the hippocampus only food deprivation caused an increase in Fkbp5 mRNA.
Interestingly, regions with a low basal expression showed higher increase in Fkbp5 mRNA following induction than regions with high basal expression, supporting the hypothesis that GR sensitivity is, at least partly, mediated via Fkbp5. In addition, this also supports the use of Fkbp5 gene expression as a marker for GR sensitivity. In summary, we were able to give an overview of the basal expression of fkbp5 mRNA as well as to extend the findings of induction of Fkbp5 and its regulatory influence on GR sensitivity from peripheral blood to the brain.

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    • "environment interactions. In this context, studies demonstrated that food deprivation (FD) induces Fkbp5 expression in the brain (Scharf et al. 2011, Yang et al. 2012). In the study by Scharf and colleagues, FD was used as a stressor, but intuitively, changes resulting from FD may also represent a response to the metabolic challenge. "
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    Journal of Endocrinology 04/2014; 222(1). DOI:10.1530/JOE-14-0129 · 3.72 Impact Factor
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    • "It is possible that FKBP5 mRNA over-expression in the DLPFC may occur in schizophrenia and bipolar disorder cases due to hypercortisolemia, which has been described in these illnesses1011. FKBP5 gene expression is upregulated by glucocorticoids through GR in rodent and primate brain3637383940, and in squirrel monkeys, chronic hypercortisolemia is compensated for by over-expression of FKBP541. Therefore, it is possible that FKBP5 upregulation may have arisen in an attempt to ‘buffer’ chronically increased stress/cortisol in individuals in this cohort. "
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    Scientific Reports 12/2013; 3:3539. DOI:10.1038/srep03539 · 5.58 Impact Factor
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    • "In the rodent brain, FKBP5 has the highest expression levels in the hippocampus, with much lower expression in other brain regions (Scharf et al. 2011). Upon stimulation with dexamethasone or exposure to stress (restraint stress or 24 h food deprivation), FKBP5 expression is dramatically increased in a number of brain regions (Scharf et al. 2011), with the largest changes observed in the amygdala and the paraventricular nucleus. In the hippocampus, the change in expression levels is less pronounced and follows only dexamethasone administration and the more severe stressor of food deprivation. "
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