RT Journal Article
SR Electronic
T1 FKBP51 in the Oval Bed Nucleus of the Stria Terminalis Regulates Anxiety-Like Behavior
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0425-21.2021
DO 10.1523/ENEURO.0425-21.2021
VO 8
IS 6
A1 Engelhardt, Clara
A1 Tang, Fiona
A1 Elkhateib, Radwa
A1 Bordes, Joeri
A1 Brix, Lea Maria
A1 van Doeselaar, Lotte
A1 Häusl, Alexander S.
A1 Pöhlmann, Max L.
A1 Schraut, Karla
A1 Yang, Huanqing
A1 Chen, Alon
A1 Deussing, Jan M.
A1 Schmidt, Mathias V.
YR 2021
UL http://www.eneuro.org/content/8/6/ENEURO.0425-21.2021.abstract
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.