Cargando…
Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression
Retinoic acid (RA), the principal active metabolite of vitamin A, is known to be involved in stress-related disorders. However, its mechanism of action in this regard remains unclear. This study reports that, in mice, endogenous cellular RA binding protein 1 (Crabp1) is highly expressed in the hypot...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619219/ https://www.ncbi.nlm.nih.gov/pubmed/34830120 http://dx.doi.org/10.3390/ijms222212240 |
_version_ | 1784604937238347776 |
---|---|
author | Lin, Yu-Lung Wei, Chin-Wen Lerdall, Thomas A. Nhieu, Jennifer Wei, Li-Na |
author_facet | Lin, Yu-Lung Wei, Chin-Wen Lerdall, Thomas A. Nhieu, Jennifer Wei, Li-Na |
author_sort | Lin, Yu-Lung |
collection | PubMed |
description | Retinoic acid (RA), the principal active metabolite of vitamin A, is known to be involved in stress-related disorders. However, its mechanism of action in this regard remains unclear. This study reports that, in mice, endogenous cellular RA binding protein 1 (Crabp1) is highly expressed in the hypothalamus and pituitary glands. Crabp1 knockout (CKO) mice exhibit reduced anxiety-like behaviors accompanied by a lowered stress induced-corticosterone level. Furthermore, CRH/DEX tests show an increased sensitivity (hypersensitivity) of their feedback inhibition in the hypothalamic–pituitary–adrenal (HPA) axis. Gene expression studies show reduced FKBP5 expression in CKO mice; this would decrease the suppression of glucocorticoid receptor (GR) signaling thereby enhancing their feedback inhibition, consistent with their dampened corticosterone level and anxiety-like behaviors upon stress induction. In AtT20, a pituitary gland adenoma cell line elevating or reducing Crabp1 level correspondingly increases or decreases FKBP5 expression, and its endogenous Crabp1 level is elevated by GR agonist dexamethasone or RA treatment. This study shows, for the first time, that Crabp1 regulates feedback inhibition of the the HPA axis by modulating FKBP5 expression. Furthermore, RA and stress can increase Crabp1 level, which would up-regulate FKBP5 thereby de-sensitizing feedback inhibition of HPA axis (by decreasing GR signaling) and increasing the risk of stress-related disorders. |
format | Online Article Text |
id | pubmed-8619219 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86192192021-11-27 Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression Lin, Yu-Lung Wei, Chin-Wen Lerdall, Thomas A. Nhieu, Jennifer Wei, Li-Na Int J Mol Sci Article Retinoic acid (RA), the principal active metabolite of vitamin A, is known to be involved in stress-related disorders. However, its mechanism of action in this regard remains unclear. This study reports that, in mice, endogenous cellular RA binding protein 1 (Crabp1) is highly expressed in the hypothalamus and pituitary glands. Crabp1 knockout (CKO) mice exhibit reduced anxiety-like behaviors accompanied by a lowered stress induced-corticosterone level. Furthermore, CRH/DEX tests show an increased sensitivity (hypersensitivity) of their feedback inhibition in the hypothalamic–pituitary–adrenal (HPA) axis. Gene expression studies show reduced FKBP5 expression in CKO mice; this would decrease the suppression of glucocorticoid receptor (GR) signaling thereby enhancing their feedback inhibition, consistent with their dampened corticosterone level and anxiety-like behaviors upon stress induction. In AtT20, a pituitary gland adenoma cell line elevating or reducing Crabp1 level correspondingly increases or decreases FKBP5 expression, and its endogenous Crabp1 level is elevated by GR agonist dexamethasone or RA treatment. This study shows, for the first time, that Crabp1 regulates feedback inhibition of the the HPA axis by modulating FKBP5 expression. Furthermore, RA and stress can increase Crabp1 level, which would up-regulate FKBP5 thereby de-sensitizing feedback inhibition of HPA axis (by decreasing GR signaling) and increasing the risk of stress-related disorders. MDPI 2021-11-12 /pmc/articles/PMC8619219/ /pubmed/34830120 http://dx.doi.org/10.3390/ijms222212240 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lin, Yu-Lung Wei, Chin-Wen Lerdall, Thomas A. Nhieu, Jennifer Wei, Li-Na Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression |
title | Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression |
title_full | Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression |
title_fullStr | Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression |
title_full_unstemmed | Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression |
title_short | Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression |
title_sort | crabp1 modulates hpa axis homeostasis and anxiety-like behaviors by altering fkbp5 expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619219/ https://www.ncbi.nlm.nih.gov/pubmed/34830120 http://dx.doi.org/10.3390/ijms222212240 |
work_keys_str_mv | AT linyulung crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression AT weichinwen crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression AT lerdallthomasa crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression AT nhieujennifer crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression AT weilina crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression |