Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice

Background: glucocorticoids may play an important role in the formation of fear memory, which is relevant to the neurobiology of post-traumatic stress disorder (PTSD). In our previous study, we showed the glucocorticoid receptor (GR) forms a protein complex with FKBP51, which prevents translocation...

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Main Authors: Yun Li, Bin Zhang, Youhua Yang, Ping Su, James Nicholas Samsom, Albert H. C. Wong, Fang Liu
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/13/24/2041
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author Yun Li
Bin Zhang
Youhua Yang
Ping Su
James Nicholas Samsom
Albert H. C. Wong
Fang Liu
author_facet Yun Li
Bin Zhang
Youhua Yang
Ping Su
James Nicholas Samsom
Albert H. C. Wong
Fang Liu
author_sort Yun Li
collection DOAJ
description Background: glucocorticoids may play an important role in the formation of fear memory, which is relevant to the neurobiology of post-traumatic stress disorder (PTSD). In our previous study, we showed the glucocorticoid receptor (GR) forms a protein complex with FKBP51, which prevents translocation of GR into the nucleus to affect gene expression; this complex is elevated in PTSD patients and by fear-conditioned learning in mice, and disrupting this complex blocks the storage and retrieval of fear-conditioned memories. The timing of release of glucocorticoid relative to the formation of a traumatic memory could be important in this process, and remains poorly understood. Methods and Results: we mapped serum corticosterone over time after fear conditioning in cardiac blood samples from male and female mice, as well as adult and aged mice using ELISA. We show a significant alteration in serum corticosterone after conditioning; notably, levels spike after 30 min but drop lower than unconditioned controls after 24 h. We further investigate the effect of glucocorticoid on GR phosphorylation and localization in HEK 293T cells by Western blot. Hydrocortisone treatment promotes phosphorylation and nuclear translocation of GR. Conclusions: these data contribute to our understanding of the processes linking stress responses to molecular signals and fear memory, which is relevant to understanding the shared mechanisms related to PTSD.
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spelling doaj-art-7c74a28728a944708ccc65ec54ebc7d02025-08-20T02:53:19ZengMDPI AGCells2073-44092024-12-011324204110.3390/cells13242041Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in MiceYun Li0Bin Zhang1Youhua Yang2Ping Su3James Nicholas Samsom4Albert H. C. Wong5Fang Liu6Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100054, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Institute of Mental Health and Drug Discovery, School of Mental Health, Wenzhou Medical University, Ouhai District, Wenzhou 325000, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Institute of Mental Health and Drug Discovery, School of Mental Health, Wenzhou Medical University, Ouhai District, Wenzhou 325000, ChinaLaboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100054, ChinaCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, CanadaCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, CanadaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Institute of Mental Health and Drug Discovery, School of Mental Health, Wenzhou Medical University, Ouhai District, Wenzhou 325000, ChinaBackground: glucocorticoids may play an important role in the formation of fear memory, which is relevant to the neurobiology of post-traumatic stress disorder (PTSD). In our previous study, we showed the glucocorticoid receptor (GR) forms a protein complex with FKBP51, which prevents translocation of GR into the nucleus to affect gene expression; this complex is elevated in PTSD patients and by fear-conditioned learning in mice, and disrupting this complex blocks the storage and retrieval of fear-conditioned memories. The timing of release of glucocorticoid relative to the formation of a traumatic memory could be important in this process, and remains poorly understood. Methods and Results: we mapped serum corticosterone over time after fear conditioning in cardiac blood samples from male and female mice, as well as adult and aged mice using ELISA. We show a significant alteration in serum corticosterone after conditioning; notably, levels spike after 30 min but drop lower than unconditioned controls after 24 h. We further investigate the effect of glucocorticoid on GR phosphorylation and localization in HEK 293T cells by Western blot. Hydrocortisone treatment promotes phosphorylation and nuclear translocation of GR. Conclusions: these data contribute to our understanding of the processes linking stress responses to molecular signals and fear memory, which is relevant to understanding the shared mechanisms related to PTSD.https://www.mdpi.com/2073-4409/13/24/2041corticosteronecortisolglucocorticoid receptorfear conditioning
spellingShingle Yun Li
Bin Zhang
Youhua Yang
Ping Su
James Nicholas Samsom
Albert H. C. Wong
Fang Liu
Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice
Cells
corticosterone
cortisol
glucocorticoid receptor
fear conditioning
title Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice
title_full Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice
title_fullStr Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice
title_full_unstemmed Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice
title_short Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice
title_sort sex and age differences in glucocorticoid signaling after an aversive experience in mice
topic corticosterone
cortisol
glucocorticoid receptor
fear conditioning
url https://www.mdpi.com/2073-4409/13/24/2041
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