The FK506 binding protein 5 (FKBP5) is a co-chaperone that regulates the activity of the glucocorticoid receptor (GR) and has been reported to mediate stress resilience. This study aimed to determine the effects of Fkbp5 deletion on acute stress-induced recognition memory impairment and hippocampal GR signaling. Wild-type and Fkbp5 -knockout mice were subjected to acute uncontrollable stress induced by restraint and electrical tail shock. First, we assessed the cognitive status of mice using a novel object recognition task. Next, we measured plasma corticosterone, GR levels, and the levels of GR phosphorylation at serine 211 in the hippocampus. Wild-type mice exhibited stress-induced memory impairments, whereas Fkbp5 -knockout mice did not. Plasma corticosterone and GR levels did not differ between the non-stressed wild-type and Fkbp5 -knockout mice, but the levels of phosphorylated GR were lower in Fkbp5 -knockout mice than in wild-type mice. Wild-type and Fkbp5 -knockout mice showed increased nuclear GR levels following stress, indicating GR translocation. However, cytosolic phosphorylated GR levels were lower in the hippocampi of Fkbp5 -knockout mice following stress than in those of wild-type mice. These results suggest that FKBP5 deficiency increases resilience to acute stress by altering GR signaling.
Bibliographical noteFunding Information:
This work was supported by grants from the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and was funded by the Korean government (Ministry of Science and ICT) (2020M3E5D9080734 to J.-S.H.).
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- Glucocorticoid receptor