PT  - JOURNAL ARTICLE
AU  - Clara Engelhardt
AU  - Fiona Tang
AU  - Radwa Elkhateib
AU  - Joeri Bordes
AU  - Lea Maria Brix
AU  - Lotte van Doeselaar
AU  - Alexander S. Häusl
AU  - Max L. Pöhlmann
AU  - Karla Schraut
AU  - Huanqing Yang
AU  - Alon Chen
AU  - Jan M. Deussing
AU  - Mathias V. Schmidt
TI  - FKBP51 in the Oval Bed Nucleus of the Stria Terminalis Regulates Anxiety-Like Behavior
AID  - 10.1523/ENEURO.0425-21.2021
DP  - 2021 Nov 01
TA  - eneuro
PG  - ENEURO.0425-21.2021
VI  - 8
IP  - 6
4099  - http://www.eneuro.org/content/8/6/ENEURO.0425-21.2021.short
4100  - http://www.eneuro.org/content/8/6/ENEURO.0425-21.2021.full
SO  - eNeuro2021 Nov 01; 8
AB  - The cochaperone FKBP51, encoded by the Fkbp5 gene, has been identified as central risk factor for anxiety-related disorders and stress system dysregulation. In the brain, the oval bed nucleus of the stria terminalis (ovBNST) has been implicated in stress-induced anxiety. However, the role of Fkbp5 in the ovBNST and its impact on anxiety-like behavior have remained unknown. Here, we show in mice that Fkbp5 in the ovBNST is reactive to acute stress and coexpressed with the stress-regulated neuropeptides Tac2 and Crh. Subsequently, results obtained from viral-mediated manipulation indicate that Fkbp5 overexpression (OE) in the ovBNST results in an anxiolytic-like tendency regarding behavior and endocrinology, whereas a Fkbp5 knock-out (KO) exposed a clear anxiogenic phenotype, indicating that native ovBNST expression and regulation is necessary for normal anxiety-related behavior. Notably, our data suggests that a stress-induced increase of Fkbp5 in the ovBNST may in fact have a protective role, leading to a transient decrease in anxiety and suppression of a future stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation. Together, our findings provide a first insight into the previously unknown relationship and effects of Fkbp5 and the ovBNST on anxiety-like behavior and HPA axis functioning.