Chronic adolescent stress alters GR-FKBP5 interactions in the hippocampus of adult female rats
AbstractChronic stress exposure during development can have lasting behavioral consequences that differ in males and females. More specifically, increased depressive behaviors in females, but not males, are observed in both humans and rodent models of chronic stress. Despite these known stress-induc...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Stress |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/10253890.2024.2312467 |
| _version_ | 1797231321903267840 |
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| author | Sydney Rowson Mandakh Bekhbat Sean Kelly Molly M. Hyer Samya Dyer David Weinshenker Gretchen Neigh |
| author_facet | Sydney Rowson Mandakh Bekhbat Sean Kelly Molly M. Hyer Samya Dyer David Weinshenker Gretchen Neigh |
| author_sort | Sydney Rowson |
| collection | DOAJ |
| description | AbstractChronic stress exposure during development can have lasting behavioral consequences that differ in males and females. More specifically, increased depressive behaviors in females, but not males, are observed in both humans and rodent models of chronic stress. Despite these known stress-induced outcomes, the molecular consequences of chronic adolescent stress in the adult brain are less clear. The stress hormone corticosterone activates the glucocorticoid receptor, and activity of the receptor is regulated through interactions with co-chaperones—such as the immunophilin FK506 binding proteins 5 (FKBP5). Previously, it has been reported that the adult stress response is modified by a history of chronic stress; therefore, the current study assessed the impact of chronic adolescent stress on the interactions of the glucocorticoid receptor (GR) with its regulatory co-chaperone FKBP5 in response to acute stress in adulthood. Although protein presence for FKBP5 did not differ by group, assessment of GR-FKBP5 interactions demonstrated that adult females with a history of chronic adolescent stress had elevated GR-FKBP5 interactions in the hippocampus following an acute stress challenge which could potentially contribute to a reduced translocation pattern given previous literature describing the impact of FKBP5 on GR activity. Interestingly, the altered co-chaperone interactions of the GR in the stressed female hippocampus were not coupled to an observable difference in transcription of GR-regulated genes. Together, these studies show that chronic adolescent stress causes lasting changes to co-chaperone interactions with the glucocorticoid receptor following stress exposure in adulthood and highlight the potential role that FKBP5 plays in these modifications. Understanding the long-term implications of adolescent stress exposure will provide a mechanistic framework to guide the development of interventions for adult disorders related to early life stress exposures. |
| first_indexed | 2024-04-24T15:42:32Z |
| format | Article |
| id | doaj.art-2c6c0a3909b0480e81ed8769067efb7e |
| institution | Directory Open Access Journal |
| issn | 1025-3890 1607-8888 |
| language | English |
| last_indexed | 2024-04-24T15:42:32Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Stress |
| spelling | doaj.art-2c6c0a3909b0480e81ed8769067efb7e2024-04-01T18:24:43ZengTaylor & Francis GroupStress1025-38901607-88882024-12-0127110.1080/10253890.2024.2312467Chronic adolescent stress alters GR-FKBP5 interactions in the hippocampus of adult female ratsSydney Rowson0Mandakh Bekhbat1Sean Kelly2Molly M. Hyer3Samya Dyer4David Weinshenker5Gretchen Neigh6Molecular and Systems Pharmacology Graduate Program, Emory University, Atlanta, GA, USANeuroscience Graduate Program, Emory University, Atlanta, GA, USADepartment of Physiology, Emory University, Atlanta, GA, USADepartment of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USADepartment of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USADepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USADepartment of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USAAbstractChronic stress exposure during development can have lasting behavioral consequences that differ in males and females. More specifically, increased depressive behaviors in females, but not males, are observed in both humans and rodent models of chronic stress. Despite these known stress-induced outcomes, the molecular consequences of chronic adolescent stress in the adult brain are less clear. The stress hormone corticosterone activates the glucocorticoid receptor, and activity of the receptor is regulated through interactions with co-chaperones—such as the immunophilin FK506 binding proteins 5 (FKBP5). Previously, it has been reported that the adult stress response is modified by a history of chronic stress; therefore, the current study assessed the impact of chronic adolescent stress on the interactions of the glucocorticoid receptor (GR) with its regulatory co-chaperone FKBP5 in response to acute stress in adulthood. Although protein presence for FKBP5 did not differ by group, assessment of GR-FKBP5 interactions demonstrated that adult females with a history of chronic adolescent stress had elevated GR-FKBP5 interactions in the hippocampus following an acute stress challenge which could potentially contribute to a reduced translocation pattern given previous literature describing the impact of FKBP5 on GR activity. Interestingly, the altered co-chaperone interactions of the GR in the stressed female hippocampus were not coupled to an observable difference in transcription of GR-regulated genes. Together, these studies show that chronic adolescent stress causes lasting changes to co-chaperone interactions with the glucocorticoid receptor following stress exposure in adulthood and highlight the potential role that FKBP5 plays in these modifications. Understanding the long-term implications of adolescent stress exposure will provide a mechanistic framework to guide the development of interventions for adult disorders related to early life stress exposures.https://www.tandfonline.com/doi/10.1080/10253890.2024.2312467Stressadolescencesex differenceFKBP5glucocorticoid |
| spellingShingle | Sydney Rowson Mandakh Bekhbat Sean Kelly Molly M. Hyer Samya Dyer David Weinshenker Gretchen Neigh Chronic adolescent stress alters GR-FKBP5 interactions in the hippocampus of adult female rats Stress Stress adolescence sex difference FKBP5 glucocorticoid |
| title | Chronic adolescent stress alters GR-FKBP5 interactions in the hippocampus of adult female rats |
| title_full | Chronic adolescent stress alters GR-FKBP5 interactions in the hippocampus of adult female rats |
| title_fullStr | Chronic adolescent stress alters GR-FKBP5 interactions in the hippocampus of adult female rats |
| title_full_unstemmed | Chronic adolescent stress alters GR-FKBP5 interactions in the hippocampus of adult female rats |
| title_short | Chronic adolescent stress alters GR-FKBP5 interactions in the hippocampus of adult female rats |
| title_sort | chronic adolescent stress alters gr fkbp5 interactions in the hippocampus of adult female rats |
| topic | Stress adolescence sex difference FKBP5 glucocorticoid |
| url | https://www.tandfonline.com/doi/10.1080/10253890.2024.2312467 |
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