Chronic stress exposure, diurnal cortisol slope, and implications for mood and fatigue: Moderation by multilocus HPA-Axis genetic variation

2019 ◽  
Vol 100 ◽  
pp. 156-163 ◽  
Author(s):  
Lisa R. Starr ◽  
Kimberly Dienes ◽  
Y. Irina Li ◽  
Zoey A. Shaw
Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2942-2952 ◽  
Author(s):  
Chantelle L. Ferland ◽  
Erin P. Harris ◽  
Mai Lam ◽  
Laura A. Schrader

Evidence suggests that when presented with novel acute stress, animals previously exposed to chronic homotypic or heterotypic stressors exhibit normal or enhanced hypothalamic-pituitary-adrenal (HPA) response compared with animals exposed solely to that acute stressor. The molecular mechanisms involved in this effect remain unknown. The extracellular signal-regulated kinase (ERK) is one of the key pathways regulated in the hippocampus in both acute and chronic stress. The aim of this study was to examine the interaction of prior chronic stress, using the chronic variable stress model (CVS), with exposure to a novel acute stressor (2,5-dihydro-2,4,5-trimethyl thiazoline; TMT) on ERK activation, expression of the downstream protein BCL-2, and the glucocorticoid receptor co-chaperone BAG-1 in control and chronically stressed male rats. TMT exposure after chronic stress resulted in a significant interaction of chronic and acute stress in all 3 hippocampus subregions on ERK activation and BCL-2 expression. Significantly, acute stress increased ERK activation, BCL-2 and BAG-1 protein expression in the dentate gyrus (DG) of CVS-treated rats compared with control, CVS-treated alone, and TMT-only animals. Furthermore, CVS significantly increased ERK activation in medial prefrontal cortex, but acute stress had no significant effect. Inhibition of corticosterone synthesis with metyrapone had no significant effect on ERK activation in the hippocampus; therefore, glucocorticoids alone do not mediate the molecular effects. Finally, because post-translational modifications of histones are believed to play an important role in the stress response, we examined changes in histone acetylation. We found that, in general, chronic stress decreased K12H4 acetylation, whereas acute stress increased acetylation. These results indicate a molecular mechanism by which chronic stress-induced HPA axis plasticity can lead to neurochemical alterations in the hippocampus that influence reactivity to subsequent stress exposure. This may represent an important site of dysfunction that contributes to stress-induced pathology such as depression, anxiety disorders, and posttraumatic stress disorder.


2012 ◽  
Vol 1 (4) ◽  
pp. 199-207 ◽  
Author(s):  
Femke Rutters ◽  
Susanne La Fleur ◽  
Sofie Lemmens ◽  
Jurriaan Born ◽  
Mieke Martens ◽  
...  

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1682 ◽  
Author(s):  
Wei Luo ◽  
Meixia Fang ◽  
Haiping Xu ◽  
Huijie Xing ◽  
Jiangnan Fu ◽  
...  

MicoRNAs (miRNAs), usually as gene regulators, participate in various biological processes, including stress responses. The hypothalamus–pituitary–adrenal axis (HPA axis) is an important pathway in regulating stress response. Although the mechanism that HPA axis regulates stress response has been basically revealed, the knowledge that miRNAs regulate stress response within HPA axis, still remains poor. The object of this study was to investigate the miRNAs in the pituitary and adrenal cortex that regulate chronic stress response with high-throughput sequencing. The pituitary and adrenal cortex of beagles and Chinese Field dogs (CFD) from a stress exposure group (including beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)) and a control group (including beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)), were selected for miRNA-seq comparisons. Comparisons, that were made in pituitary (including BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1 and BP2 vs. CFDP2) and adrenal cortex (including BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2), showed that a total of 39 and 18 common differentially expressed miRNAs (DE-miRNAs) (Total read counts > 1,000, Fold change > 2 &p-value < 0.001), that shared in at least two pituitary comparisons and at least two adrenal cortex comparisons, were detected separately. These identified DE-miRNAs were predicted for target genes, thus resulting in 3,959 and 4,010 target genes in pituitary and adrenal cortex, respectively. Further, 105 and 10 differentially expressed genes (DEGs) (Fold change > 2 &p-value < 0.05) from those target genes in pituitary and adrenal cortex were obtained separately, in combination with our previous corresponding transcriptome study. Meanwhile, in line with that miRNAs usually negatively regulated their target genes and the dual luciferase reporter assay, we finally identified cfa-miR-205 might play an important role by upregulatingMMDin pituitary and hippocampus, thus enhancing the immune response, under chronic stress exposure. Our results shed light on the miRNA expression profiles in the pituitary and adrenal cortex with and without chronic stress exposure, and provide a new insight into miR-205 with its feasible role in regulating chronic stress in the pituitary and hippocampus through targetingMMD.


2018 ◽  
Vol 31 (04) ◽  
pp. 1339-1352 ◽  
Author(s):  
Lisa R. Starr ◽  
Meghan Huang

AbstractResearch suggests that genetic variants linked to hypothalamic-pituitary-adrenal (HPA)-axis functioning moderate the association between environmental stressors and depression, but examining gene–environment interactions with single polymorphisms limits power. The current study used a multilocus genetic profile score (MGPS) approach to measuring HPA-axis–related genetic variation and examined interactions with acute stress, chronic stress, and childhood adversity (assessed using contextual threat interview methods) with depressive symptoms as outcomes in an adolescent sample (ages 14–17, N = 241; White subsample n = 192). Additive MGPSs were calculated using 10 single nucleotide polymorphisms within HPA-axis genes (CRHR1, NR3C2, NR3C1, FKBP5). Higher MGPS directly correlated with adolescent depressive symptoms. Moreover, MGPS predicted stronger associations between acute and chronic stress and adolescent depressive symptoms and also moderated the effect of interpersonal, but not noninterpersonal, childhood adversity. Gene–environment interactions individually accounted for 5%–8% of depressive symptom variation. All results were retained following multiple test correction and stratification by race. Results suggest that using MGPSs provides substantial power to examine gene–environmental interactions linked to affective outcomes among adolescents.


2021 ◽  
Vol 15 ◽  
Author(s):  
Sydney A. Rowson ◽  
Kristen E. Pleil

The paraventricular nucleus of the thalamus (PVT) is a critical neural hub for the regulation of a variety of motivated behaviors, integrating stress and reward information from environmental stimuli to guide discrete behaviors via several limbic projections. Neurons in the PVT are activated by acute and chronic stressors, however several roles of the PVT in behavior modulation emerge only following repeated stress exposure, pointing to a role for hypothalamic pituitary adrenal (HPA) axis modulation of PVT function. Further, there may be a reciprocal relationship between the PVT and HPA axis in which chronic stress-induced recruitment of the PVT elicits an additional role for the PVT to regulate motivated behavior by modulating HPA physiology and thus the neuroendocrine response to stress itself. This complex interaction may make the PVT and its role in influencing motivated behavior particularly susceptible to chronic stress-induced plasticity in the PVT, especially in females who display increased susceptibility to stress-induced maladaptive behaviors associated with neuropsychiatric diseases. Though literature is describing the sex-specific effects of acute and chronic stress exposure on HPA axis activation and motivated behaviors, the impact of sex on the role of the PVT in modulating the behavioral and neuroendocrine response to stress is less well established. Here, we review what is currently known regarding the acute and chronic stress-induced activation and behavioral role of the PVT in male and female rodents. We further explore stress hormone and neuropeptide signaling mechanisms by which the HPA axis and PVT interact and discuss the implications for sex-dependent effects of chronic stress on the PVT’s role in motivated behaviors.


2019 ◽  
Vol 10 (1) ◽  
pp. 277-288 ◽  
Author(s):  
Wanxiu Cao ◽  
Chengcheng Wang ◽  
Yaoxian Chin ◽  
Xin Chen ◽  
Yuan Gao ◽  
...  

DHA-PL and EPA-PL may effectively protect mice against intestinal dysfunction under chronic stress exposure.


2019 ◽  
Vol 102 ◽  
pp. 139-148 ◽  
Author(s):  
Kelly E. Rentscher ◽  
Judith E. Carroll ◽  
Rena L. Repetti ◽  
Steve W. Cole ◽  
Bridget M. Reynolds ◽  
...  

2021 ◽  
Author(s):  
Yang Yang ◽  
Wanwan Han ◽  
Aijia Zhang ◽  
Mindie Zhao ◽  
Wei Cong ◽  
...  

Abstract Corticotropin-releasing hormone (CRH), the major secretagogue of the hypothalamic-pituitary-adrenal (HPA) axis, is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions. N6-methyladenosine (m6A) RNA methylation is involved in the regulation of circadian rhythm, yet it remains unknown whether CRH expression and m6A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress. Here, we show that chronic exposure to corticosterone (CORT) eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken. The circadian rhythms of clock genes in hippocampus, hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens. The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened, together with mRNA of other feeding-related neuropeptides. Interestingly, hypothalamic m6A level oscillates in an opposite pattern to CRH mRNA, with lowest m6A level after midnight (ZT18) corresponding to the peak of CRH mRNA before dawn (ZT22). CORT diminished the circadian rhythm of m6A methylation with significantly increased level at night. Further site-specific m6A analysis on 3’UTR of CRH mRNA indicates that higher m6A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night (ZT18 and ZT22). Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus, leading to dysfunction of HPA axis in the chicken. RNA m6A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions.


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