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...

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Autores principales:	Yu-Lung Lin, Chin-Wen Wei, Thomas A. Lerdall, Jennifer Nhieu, Li-Na Wei
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Crabp1 anxiety HPA axis retinoic acid stress FKBP5 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/388a3bb4bf3146c09567ed23593afeac
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spelling	oai:doaj.org-article:388a3bb4bf3146c09567ed23593afeac2021-11-25T17:54:36ZCrabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression10.3390/ijms2222122401422-00671661-6596https://doaj.org/article/388a3bb4bf3146c09567ed23593afeac2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12240https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Retinoic 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.Yu-Lung LinChin-Wen WeiThomas A. LerdallJennifer NhieuLi-Na WeiMDPI AGarticleCrabp1anxietyHPA axisretinoic acidstressFKBP5Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12240, p 12240 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Crabp1 anxiety HPA axis retinoic acid stress FKBP5 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Crabp1 anxiety HPA axis retinoic acid stress FKBP5 Biology (General) QH301-705.5 Chemistry QD1-999 Yu-Lung Lin Chin-Wen Wei Thomas A. Lerdall Jennifer Nhieu Li-Na Wei Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression
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	article
author	Yu-Lung Lin Chin-Wen Wei Thomas A. Lerdall Jennifer Nhieu Li-Na Wei
author_facet	Yu-Lung Lin Chin-Wen Wei Thomas A. Lerdall Jennifer Nhieu Li-Na Wei
author_sort	Yu-Lung Lin
title	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_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_sort	crabp1 modulates hpa axis homeostasis and anxiety-like behaviors by altering fkbp5 expression
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/388a3bb4bf3146c09567ed23593afeac
work_keys_str_mv	AT yulunglin crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression AT chinwenwei crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression AT thomasalerdall crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression AT jennifernhieu crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression AT linawei crabp1modulateshpaaxishomeostasisandanxietylikebehaviorsbyalteringfkbp5expression
_version_	1718411857478287360

Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression

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