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

2021 ◽  
Vol 22 (22) ◽  
pp. 12240
Author(s):  
Yu-Lung Lin ◽  
Chin-Wen Wei ◽  
Thomas A. Lerdall ◽  
Jennifer Nhieu ◽  
Li-Na Wei
Keyword(s):  
Hpa Axis ◽  
Active Metabolite ◽  
Feedback Inhibition ◽  
Corticosterone Level ◽  
Stress Induction ◽  
Expression Studies ◽  
Pituitary Glands ◽  
Increased Sensitivity ◽  
Gene Expression Studies ◽  
First Time

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.

scholarly journals Differential Adaptive Responses to Chronic Stress of Maternally Stressed Male Mice Offspring

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 3202-3210 ◽  
Author(s):  
Sooyoung Chung ◽  
Gi Hoon Son ◽  
Sung Ho Park ◽  
Eonyoung Park ◽  
Kun Ho Lee ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Acute Stress ◽  
Feedback Inhibition ◽  
Corticosterone Level ◽  
Dependent Manner ◽  
Male Mice ◽  
Adaptive Responses ◽  
Repeated Restraint Stress ◽  
Postnatal Stress

Abstract It is well established that stress in early life can alter the activity of the hypothalamus-pituitary-adrenal (HPA) axis, but most studies to date have focused on HPA reactivity in response to a single acute stress. The present study addressed whether stress in pregnant mice could influence the adaptive responses of their offspring to chronic stress. Male offspring were exclusively used in this study. Elevated plus maze tests revealed that 14 d of repeated restraint stress (6 h per day; from postnatal d 50–63) significantly increased anxiety-like behavior in maternally stressed mice. NBI 27914, a CRH receptor antagonist, completely eliminated anxiety-related behaviors in a dose-dependent manner, indicating an involvement of a hyperactive CRH system. In accordance with increased anxiety, CRH contents in the hypothalamus and amygdala were significantly higher in these mice. Despite an increased basal activity of the CRH-ACTH system, the combination of chronic prenatal and postnatal stress resulted in a significant reduction of basal plasma corticosterone level, presumably because of a defect in adrenal function. Along with alterations in hypothalamic and hippocampal corticosteroid receptors, it was also demonstrated that a dysfunction in negative feedback inhibition of the HPA axis could be deteriorated by chronic stress in maternally stressed male mice. Taken together, these results indicate that exposure to maternal stress in the womb can affect an animal’s coping capacity to chronic postnatal stress.

Insight into molecular pathways of retinal metabolism, associated with vitellogenesis in zebrafish

2012 ◽  
Vol 302 (6) ◽  
pp. E626-E644 ◽  
Author(s):  
Liraz Levi ◽  
Tamar Ziv ◽  
Arie Admon ◽  
Berta Levavi-Sivan ◽  
Esther Lubzens
Keyword(s):  
Gene Expression ◽  
Circulatory System ◽  
Hormone Response Elements ◽  
Bioinformatic Tools ◽  
Expression Studies ◽  
Vitellogenin Synthesis ◽  
17Β Estradiol ◽  
Extrahepatic Tissues ◽  
Gene Expression Studies ◽  
First Time

Retinal is the main retinoid stored in oviparous eggs of fish, amphibians, and reptiles, reaching the oocytes in association with vitellogenins, the yolk precursor proteins. During early presegmentation stages of zebrafish embryos, retinal is metabolized to retinoic acid (RA), which regulates genes involved in cell proliferation, differentiation, and tissue function and is therefore essential for normal embryonic development. While synthesis of vitellogenin and its regulation by 17β-estradiol (E2) were extensively investigated, pathways for retinal synthesis remain obscure. We determined the expression pattern of 46 candidate genes, aiming at identifying enzymes associated with retinal synthesis, ascertaining whether they were regulated by E2, and finding pathways that could fulfill the demand for retinoids during vitellogenesis. Genes associated with retinal synthesis were upregulated in liver ( rdh10, rdh13, sdr) and surprisingly also in intestine ( rdh13) and ovary ( rdh1, sdr), concomitantly with higher gene expression and synthesis of vitellogenins in liver but also in extrahepatic tissues, shown here for the first time. Vitellogenin synthesis in the ovary was regulated by E2. Gene expression studies suggest that elevated retinal synthesis in liver, intestine, and ovary also depends on cleavage of carotenoids (by Bcdo2 or Bmco1), but in the ovary it may also be contingent on higher uptake of retinol from the circulatory system (via Stra6) and retinol synthesis from retinyl esters (by Lpl). Decrease in oxidation (by Raldh2 or Raldh3) of retinal to RA and/or degradation of RA (by Cyp26a1) may also facilitate higher hepatic retinal levels. Together, these processes enable meeting the putative demands of retinal for binding to vitellogenins. Bioinformatic tools reveal multiple hormone response elements in the studied genes, suggesting complex and intricate regulation of these processes.

scholarly journals GPER-Deficient Rats Exhibit Lower Serum Corticosterone Level and Increased Anxiety-Like Behavior

2020 ◽  
Vol 2020 ◽  
pp. 1-22 ◽  
Author(s):  
Yi Zheng ◽  
Meimei Wu ◽  
Ting Gao ◽  
Li Meng ◽  
Xiaowei Ding ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Corticosterone Level ◽  
Brain Structures ◽  
Ample Evidence ◽  
Genetic Ablation ◽  
Serum Corticosterone ◽  
Underlying Mechanisms ◽  
G Protein Coupled ◽  
Prolonged Stress

Ample evidence suggests that estrogens have strong influences on the occurrence of stress-related mood disorders, but the underlying mechanisms remain poorly understood. Through multiple approaches, we demonstrate that the G protein-coupled estrogen receptor (GPER) is widely distributed along the HPA axis and in brain structures critically involved in mood control. Genetic ablation of GPER in the rat resulted in significantly lower basal serum corticosterone level but enhanced ACTH release in response to acute restraint stress, especially in the female. GPER-/- rats of either sex displayed increased anxiety-like behaviors and deficits in learning and memory. Additionally, GPER deficiency led to aggravation of anxiety-like behaviors following single-prolonged stress (SPS). SPS caused significant decreases in serum corticosterone in WT but not in GPER-deficient rats. The results highlight an important role of GPER at multiple sites in regulation of the HPA axis and mood.

scholarly journals Assessment of common housekeeping genes as reference for gene expression studies using RT-qPCR in mouse choroid plexus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kim Hoa Ho ◽  
Annarita Patrizi
Keyword(s):  
Gene Expression ◽  
Choroid Plexus ◽  
Sensory Deprivation ◽  
Housekeeping Genes ◽  
Housekeeping Gene ◽  
Experimental Conditions ◽  
Brain Repair ◽  
Expression Studies ◽  
Testing Algorithms ◽  
Gene Expression Studies

AbstractChoroid plexus (ChP), a vascularized secretory epithelium located in all brain ventricles, plays critical roles in development, homeostasis and brain repair. Reverse transcription quantitative real-time PCR (RT-qPCR) is a popular and useful technique for measuring gene expression changes and also widely used in ChP studies. However, the reliability of RT-qPCR data is strongly dependent on the choice of reference genes, which are supposed to be stable across all samples. In this study, we validated the expression of 12 well established housekeeping genes in ChP in 2 independent experimental paradigms by using popular stability testing algorithms: BestKeeper, DeltaCq, geNorm and NormFinder. Rer1 and Rpl13a were identified as the most stable genes throughout mouse ChP development, while Hprt1 and Rpl27 were the most stable genes across conditions in a mouse sensory deprivation experiment. In addition, Rpl13a, Rpl27 and Tbp were mutually among the top five most stable genes in both experiments. Normalisation of Ttr and Otx2 expression levels using different housekeeping gene combinations demonstrated the profound effect of reference gene choice on target gene expression. Our study emphasized the importance of validating and selecting stable housekeeping genes under specific experimental conditions.

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