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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lin, Yu-Lung, Wei, Chin-Wen, Lerdall, Thomas A., Nhieu, Jennifer, Wei, Li-Na
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