Journal Article

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

Müller, Marianne B., Binder, Elisabeth B., Liebl, Claudia, Scharf, Sebastian H., Schmidt, Mathias V.

2011

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Affective disorders / Amygdala / Animal cognition / Animals / Antidepressants / Asthma / Bioassays / Biology / Biomarkers / Blood / Brain / Brain - drug effects / Brain - metabolism / Brain - physiology / Brain research / Central nervous system / Deoxyribonucleic acid / Deprivation / Dexamethasone / Dexamethasone - pharmacology / Dietary restrictions / DNA / Experiments / Feedback / Food Deprivation / Gene expression / Gene Expression Regulation - drug effects / Genes / Glucocorticoids / Glucocorticoids - pharmacology / Hippocampus / Hormones / House mouse / Hypothalamic-pituitary-adrenal axis / Hypothalamus / Laboratory animals / Male / Medical research / Medicine / Mental depression / Messenger RNA / Mice / Mice, Inbred C57BL / Neurosciences / Paraventricular nucleus / Peripheral blood / Physiology / Pituitary / Protein binding / Proteins / Psychiatry / Respiratory diseases / Risk factors / RNA, Messenger - genetics / RNA, Messenger - metabolism / Sensitivity / Stress / Stress, Physiological - drug effects / Stress, Physiological - genetics / Stresses / Studies / Tacrolimus / Tacrolimus Binding Proteins - genetics / Tacrolimus-binding protein