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

Neuroscience. 2022 Feb 10:483:95-103. doi: 10.1016/j.neuroscience.2021.12.020. Epub 2021 Dec 17.

Abstract

FK501 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 post-traumatic 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.

Keywords: FKBP5; corticosterone; glucocorticoid receptor; hippocampus; synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Hippocampus / metabolism
  • Mice
  • Pituitary-Adrenal System / metabolism
  • Receptors, Glucocorticoid* / metabolism
  • Stress, Psychological / metabolism
  • Synaptic Transmission
  • Tacrolimus Binding Proteins*

Substances

  • Carrier Proteins
  • Receptors, Glucocorticoid
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5