• KSBNS 2024


Original Article

Exp Neurobiol 2023; 32(2): 91-101

Published online April 30, 2023

© The Korean Society for Brain and Neural Sciences

Intact Recognition Memory and Altered Hippocampal Glucocorticoid Receptor Signaling in Fkbp5-deficient Mice Following Acute Uncontrollable Stress

Yong-Jae Jeon1†, Bo-Ryoung Choi1†, Min-Sun Park1, Yoon-Sun Jang1, Sujung Yoon2, In Kyoon Lyoo2,3 and Jung-Soo Han1*

1Department of Biological Sciences, Konkuk University, Seoul 05029,
2Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul 03760,
3Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-450-3292, FAX: 82-2-3436-5432
These authors contributed equally to this article.

Received: February 17, 2023; Revised: March 15, 2023; Accepted: March 31, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Graphical Abstract

Keywords: FKBP5, Glucocorticoid receptor, Hippocampus, Memory, Mice