Interaction Between Glucocorticoid Receptors and FKBP5 in Regulating Neurotransmission of the Hippocampus

binding protein 51 (FKBP5) is a stress response prolyl isomerase that inhibits the translocation of the glucocorticoid receptor (GR) heterocomplex to the nucleus. Previous studies have shown that the expression levels of FKBP5 are positively correlated with psychiatric disorders, including depression and posttraumatic stress disorder. In rodents, FKBP5 deletion in the brain leads to be resilient to stress-induced depression. The hippocampus is known to be one of the primary locations mediating stress responses in the brain by providing negative feedback signals to the hypothalamus-pituitary-adrenal gland axis. Therefore, we aimed to investigate the role of FKBP5 and its interaction with GRs in the hippocampus. We observed that FKBP5 deletion in the hippocampus resulted in a minimal change in synaptic transmission. In the hippocampus, GR activation alters the release probability in inhibitory synapses as well as the postsynaptic contribution of glutamate receptors in excitatory synapses; however, no such alterations were induced in the absence of FKBP5. FKBP5 deficiency causes insensitivity to activated GRs in the hippocampus suggesting that FKBP5 mediates synaptic changes caused by GR activation. Our study provides electrophysiological evidence of stress resilience observed in FKBP5-deficient mice. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

FKBP5 is a protein that inhibits the translocation of the glucocorticoid receptor, and its expression is related to psychiatric disorders. Deletion of FKBP5 in the brain makes rodents resilient to stress-induced depression. Our study found that FKBP5 deletion in the hippocampus causes changes in synaptic transmission and insensitivity to activated glucocorticoid receptors.