scholarly journals Stress sensitivity is increased in transgenic rats with low brain angiotensinogen

2009 ◽  
Vol 204 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Helge Müller ◽  
Juliane Kröger ◽  
Olaf Jöhren ◽  
Silke Szymczak ◽  
Michael Bader ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Hpa Axis ◽  
Stress Responses ◽  
Forced Swim Test ◽  
Stress Sensitivity ◽  
Transgenic Rat ◽  
Mrna Levels ◽  
Stress Tests ◽  
Corticosterone Response ◽  
Corticosterone Release

AT1 blockers attenuate hypothalamo-pituitary–adrenal (HPA) axis reactivity in hypertension independently of their potency to lower blood pressure. A reduced pituitary sensitivity to CRH and a downregulation of hypothalamic CRH expression have been suggested to influence HPA axis activity during chronic AT1 blockade. This study was aimed at confirming the role of central angiotensin II in regulating HPA reactivity by using the transgenic rat TGR(ASrAOGEN), a model featuring low levels of brain angiotensinogen. Different stress tests were performed to determine HPA reactivity in TGR(ASrAOGEN) and appropriate controls. In TGR(ASrAOGEN), blood pressure was diminished compared to controls. The corticosterone response to a CRH or ACTH challenge and a forced swim test was more distinct in TGR(ASrAOGEN) than it was in controls and occurred independently of a concurrent enhancement in ACTH. Using quantitative real-time PCR, we found increased mRNA levels of melanocortin 2 (Mc2r) and AT2 receptors (Agtr2) in the adrenals of TGR(ASrAOGEN), whereas mRNA levels of Crh, Pomc, and AT1 receptors (Agtr1) remained unchanged in hypothalami and pituitary glands. Since stress responses were increased rather than attenuated in TGR(ASrAOGEN), we conclude that the reduced HPA reactivity during AT1 blockade could not be mimicked in a specific transgenic rat model featuring a centrally inactivated renin–angiotensin–aldosterone system. The ACTH independency of the enhanced corticosterone release during CRH test and the enhanced corticosterone response to ACTH rather indicates an adrenal mechanism. The upregulation of adrenal MC2 and AT2 receptors seems to be involved in the stimulated facilitation of adrenal corticosterone release for effectuating the stimulated stress responses.

Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis

1994 ◽  
Vol 141 (3) ◽  
pp. 497-503 ◽  
Author(s):  
P J Larsen ◽  
J D Mikkelsen ◽  
D Jessop ◽  
S L Lightman ◽  
H S Chowdrey
Keyword(s):  
Hpa Axis ◽  
Restraint Stress ◽  
Acute Stress ◽  
Monosodium Glutamate ◽  
Plasma Corticosterone ◽  
Mrna Levels ◽  
Plasma Acth ◽  
Corticotrophin Releasing Factor ◽  
Acute And Chronic Stress ◽  
Corticosterone Response

Abstract We have investigated the effects of monosodium glutamate (MSG) lesioning of the arcuate nucleus on both central and peripheral components of the hypothalamo-pituitary-adrenocortical (HPA) axis under basal conditions and under acute and chronic stress. Plasma ACTH levels were lower in MSG-lesioned rats (27 ± 7 pg/ml) compared with controls (71 ± 18 pg/ml) while corticosterone levels were elevated (523 ± 84 ng/ml compared with 176 ± 34 ng/ml). Quantititative in situ hybridization histochemistry revealed that corticotrophin-releasing factor mRNA levels in the medial parvocellular part of the hypothalamic paraventricular nucleus were significantly lower in MSG-treated rats. MSG lesioning resulted in an enhanced response of corticosterone to restraint stress (1309 ± 92 ng/ml compared with 628 ± 125 ng/ml in sham-lesioned animals), while ACTH responses to restraint stress in MSG-lesioned and sham-MSG groups were not significantly different (160 ± 24 pg/ml and 167 ± 24 pg/ml respectively). These data suggest that MSG-lesioned rats have an increased adrenocortical sensitivity. In rats subjected to the chronic osmotic stimulus of drinking 2% saline for 12 days, plasma ACTH levels were significantly reduced (15 ± 5 pg/ml) and the ACTH and corticosterone responses to restraint stress were eliminated. ACTH levels were also reduced in MSG-treated animals given 2% saline and the ACTH response to acute stress remained absent in these animals. However, a robust corticosterone response to restraint stress was observed in saline-treated MSG-lesioned rats. These data demonstrate that MSG lesioning results in elevated basal and stress-induced plasma corticosterone, and restores the adrenocortical response to stress which is absent in chronically osmotically stimulated rats. The evidence is consistent with the suggestion that MSG lesions a pathway involved in tonic inhibition of the HPA axis. In addition, the adrenocortical sensitivity to ACTH and other secretagogues may be increased in MSG-treated animals. Journal of Endocrinology (1994) 141, 497–503

scholarly journals Fast Feedback Inhibition of the HPA Axis by Glucocorticoids Is Mediated by Endocannabinoid Signaling

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4811-4819 ◽  
Author(s):  
Nathan K. Evanson ◽  
Jeffrey G. Tasker ◽  
Matthew N. Hill ◽  
Cecilia J. Hillard ◽  
James P. Herman
Keyword(s):  
Hpa Axis ◽  
Negative Feedback ◽  
Stress Responses ◽  
Feedback Inhibition ◽  
Signaling Mechanism ◽  
Hypothalamic Tissue ◽  
Corticosterone Release ◽  
Arachidonoyl Glycerol ◽  
Local Release ◽  
Glucocorticoid Action

Glucocorticoid hormones are secreted in response to stimuli that activate the hypothalamo-pituitary-adrenocortical (HPA) axis and self-regulate through negative feedback. Negative feedback that occurs on a rapid time scale is thought to act through nongenomic mechanisms. In these studies, we investigated fast feedback inhibition of HPA axis stress responses by direct glucocorticoid action at the paraventricular nucleus of the hypothalamus (PVN). Local infusion of dexamethasone or a membrane-impermeant dexamethasone-BSA conjugate into the PVN rapidly inhibits restraint-induced ACTH and corticosterone release in a manner consistent with feedback actions at the cell membrane. The dexamethasone fast feedback response is blocked by the cannabinoid CB1 receptor antagonist AM-251, suggesting that fast feedback requires local release of endocannabinoids. Hypothalamic tissue content of the endocannabinoid 2-arachidonoyl glycerol is elevated by restraint stress, consistent with endocannabinoid action on feedback processes. These data support the hypothesis that glucocorticoid-induced fast feedback inhibition of the HPA axis is mediated by a nongenomic signaling mechanism that involves endocannabinoid signaling at the level of the PVN.

scholarly journals TheKampoMedicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shoko Shimizu ◽  
Takashi Tanaka ◽  
Takashi Takeda ◽  
Masaya Tohyama ◽  
Shingo Miyata
Keyword(s):  
Hpa Axis ◽  
Stress Responses ◽  
Glucocorticoid Receptors ◽  
Psychological Symptoms ◽  
Plasma Corticosterone ◽  
Mrna Levels ◽  
Stress Exposure ◽  
Protein Levels ◽  
Hpa Axis Activity ◽  
The Brain

It is well known that glucocorticoid receptor (GR) signaling regulates the hypothalamic-pituitary-adrenal (HPA) axis, and GR expression level is associated with HPA axis activity. Recent studies revealed that microRNA- (miR-) 18 and/or 124a are candidate negative regulators of GR in the brain. TheKampomedicine Yokukansan (YKS) can affect psychological symptoms such as depression and anxiety that are associated with stress responses. In this study, we evaluated the effect of YKS on miR-18 and 124a and GR levels in mice exposed to stress. We found that YKS pretreatment normalized elevated plasma corticosterone levels in stress-exposed mice. In addition, GR mRNA levels were downregulated in the brain following stress exposure. While miR-124a expression levels were not altered in the hypothalamus of stress-exposed mice, miR-18 levels decreased in the hypothalamus of YKS-pretreated mice after stress exposure. Finally, GR protein levels in the paraventricular nucleus (PVN) of the hypothalamus after stress exposure recovered in YKS-pretreated mice. Collectively, these data suggest that YKS normalizes GR protein levels by regulating miR-18 expression in the hypothalamus, thus normalizing HPA axis activity following stress exposure.

scholarly journals Ketamine decreases HPA axis reactivity to a novel stressor in male but not female mice

2021 ◽  
Author(s):  
Colin J Johnston ◽  
Paul F Fitzgerald ◽  
Jena S Gewarges ◽  
Brendon O Watson ◽  
Joanna L Spencer-Segal
Keyword(s):  
Hpa Axis ◽  
Forced Swim Test ◽  
Antidepressant Drug ◽  
Drug Effects ◽  
Behavioral Effect ◽  
Neural Circuitry ◽  
Synthesis Inhibitor ◽  
Vehicle Treatment ◽  
Corticosterone Response ◽  
Adrenal Corticosterone

Ketamine is an antidepressant drug that interacts with the hypothalamic-pituitary-adrenal (HPA) axis, but whether this interaction is important for its behavioral effect is unknown. The goal of this experiment was to determine whether the behavioral response to ketamine depends on intact HPA axis function. Male and female C57BL/6J mice underwent chronic unpredictable stress prior to ketamine (30 mg/kg, i.p.) or vehicle treatment, with or without the glucocorticoid synthesis inhibitor metyrapone (20 mg/kg, i.p.) to block adrenal corticosterone production. Mice were tested in the forced swim test (FST) and open field test one and two days after injection, respectively. Fecal corticosterone was measured at select time points. No significant drug effects on behavior were observed. Males consistently had higher fecal corticosterone levels and stress-induced increases than females. Ketamine lowered the fecal corticosterone response to the FST only in males. These data show that ketamine after chronic stress decreases the corticosterone response to a novel stressor (the FST) in males, but not females. Corticosterone levels in all mice correlated with immobility in the FST, suggesting that shared neural circuitry could mediate both endocrine and behavioral responses. This circuitry may be ketamine-responsive only in males.

scholarly journals M102. MEASURING PHYSIOLOGICAL RESPONSES ASSOCIATED WITH SOCIAL STRESS IN A VIRTUAL ENVIRONMENT AND ITS RELATIONSHIP WITH CHILDHOOD TRAUMA IN EARLY SCHIZOPHRENIA - A PILOT STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S174-S174
Author(s):  
Stéfan Du Plessis ◽  
Michelle Mckenzie ◽  
Ivan Crockart ◽  
Sanja Kilian ◽  
Frederika Scheffler ◽  
...  
Keyword(s):  
Childhood Trauma ◽  
Hpa Axis ◽  
Stress Responses ◽  
Social Stress ◽  
Physiological Stress ◽  
Stress Test ◽  
Stress Sensitivity ◽  
Childhood Trauma Questionnaire ◽  
The Relationship ◽  
Fear Of Heights

Abstract Background In lower to middle income countries (LMIC), the influences of environmental stress on neurobiological processes involved in the development of schizophrenia is of great importance. High levels of stress may contribute to an increased burden of schizophrenia, including profound functional impairment and disability, decreased productivity, and even elevated mortality. Stress in Schizophrenia has been associated with behavioral disturbances such as maladaptive coping styles as well as well-established physiological abnormalities in sensorimotor gating in the form of abnormal startle responses. In turn, childhood trauma exposure is known to affect physiological stress responses. Indeed, we have found childhood trauma to be associated with both white matter and hippocampal changes in schizophrenia. Few studies, however, have explored the relationship between Childhood trauma and stress responses in schizophrenia. In recent years Virtual Reality (VR) has undergone a resurgence as a viable method for studying fear related physiological stress responses in an ecologically valid manner. Here we aim to investigate the potential relationship between abnormal physiological stress responses in schizophrenia with early life adversity. Methods Physiological response data were collected while participants completed a VR paradigm based on the Trier stress test, a well-established social stressor that reliably elicits a stress response in participants in VR and HPA axis attenuation in schizophrenia. Data were also collected in a fear of heights environment, not associated with abnormalities in schizophrenia. Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ). HPA axis stress responses during the course of the task were assessed using saliva cortisol samples collected at key points during the paradigms. Results Preliminary data of both the social anxiety and fear of heights scenario will be presented. We will focus specifically on the viability of using VR in a LMIC context. Discussion VR could prove to be a cost-effective tool to explore the relationship between childhood trauma, stress sensitivity and schizophrenia.

Selective contributions of the medial preoptic nucleus to testosterone-dependant regulation of the paraventricular nucleus of the hypothalamus and the HPA axis

2008 ◽  
Vol 295 (4) ◽  
pp. R1020-R1030 ◽  
Author(s):  
Martin Williamson ◽  
Victor Viau
Keyword(s):  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Stress Responses ◽  
Brain Regions ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Preoptic Nucleus ◽  
External Zone ◽  
Medial Preoptic Nucleus ◽  
Medial Nucleus

Previous data have consistently demonstrated an inhibitory effect of androgens on stress-induced hypothalamic-pituitary-adrenal (HPA) responses. Several brain regions may influence androgen-mediated inhibition of the HPA axis, including the medial preoptic area. To test the role of the medial preoptic nucleus (MPN) specifically, we examined in high- and low-testosterone-replaced gonadectomized rats bearing discrete bilateral lesions of the MPN basal and stress-induced indexes of HPA function, and the relative levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA in the amygdala. High testosterone replacement decreased plasma adrenocorticotropin hormone (ACTH) and paraventricular nucleus (PVN) Fos responses to restraint exposure in sham- but not in MPN-lesioned animals. AVP-, but not CRH-immunoreactivity staining in the external zone of the median eminence was increased by testosterone in sham animals, and MPN lesions blocked this increment in AVP. A similar interaction between MPN lesions and testosterone occurred on AVP mRNA levels in the medial nucleus of the amygdala. These findings support an involvement of MPN projections in mediating the AVP response to testosterone in both the medial parvocellular PVN and medial amygdala. We conclude that the MPN forms part of an integral circuit that mediates the central effects of gonadal status on neuroendocrine and central stress responses.

scholarly journals Loss of mGluR5 in D1 Receptor-Expressing Neurons Improves Stress Coping

2021 ◽  
Vol 22 (15) ◽  
pp. 7826
Author(s):  
Luca Zangrandi ◽  
Claudia Schmuckermair ◽  
Hussein Ghareh ◽  
Federico Castaldi ◽  
Regine Heilbronn ◽  
...  
Keyword(s):  
Stress Responses ◽  
Metabotropic Glutamate Receptor ◽  
Forced Swim Test ◽  
Functional Integration ◽  
D1 Receptor ◽  
Conditional Knockout ◽  
Stress Coping ◽  
Metabotropic Glutamate ◽  
Internal States

The metabotropic glutamate receptor type 5 (mGluR5) has been proposed to play a crucial role in the selection and regulation of cognitive, affective, and emotional behaviors. However, the mechanisms by which these receptors mediate these effects remain largely unexplored. Here, we studied the role of mGluR5 located in D1 receptor-expressing (D1) neurons in the manifestation of different behavioral expressions. Mice with conditional knockout (cKO) of mGluR5 in D1 neurons (mGluR5D1 cKO) and littermate controls displayed similar phenotypical profiles in relation to memory expression, anxiety, and social behaviors. However, mGluR5D1 cKO mice presented different coping mechanisms in response to acute escapable or inescapable stress. mGluR5D1 cKO mice adopted an enhanced active stress coping strategy upon exposure to escapable stress in the two-way active avoidance (TWA) task and a greater passive strategy upon exposure to inescapable stress in the forced swim test (FST). In summary, this work provides evidence for a functional integration of the dopaminergic and glutamatergic system to mediate control over internal states upon stress exposure and directly implicates D1 neurons and mGluR5 as crucial mediators of behavioral stress responses.

scholarly journals State Anxiety Is Associated with Cardiovascular Reactivity in Young, Healthy African Americans

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mildred A. Pointer ◽  
Sadiqa Yancey ◽  
Ranim Abou-Chacra ◽  
Patricia Petrusi ◽  
Sandra J. Waters ◽  
...  
Keyword(s):  
Blood Pressure ◽  
African Americans ◽  
Cardiovascular Reactivity ◽  
Trait Anxiety ◽  
State Anxiety ◽  
Blood Pressure Response ◽  
Cold Pressor ◽  
Pressure Response ◽  
Anxiety State ◽  
Stress Tests

Although several studies have shown that enhanced cardiovascular reactivity can predict hypertension development in African Americans, these findings have not been consistent among all studies examining reactivity and hypertension susceptibility. This inconsistency may be explained by the influence of anxiety (state and trait) on the blood pressure response to stress. Therefore, this study sought to determine whether anxiety is associated with blood pressure response to cold pressor (CP) and anger recall (AR) stress tests in young healthy African Americans. Modeling using state and trait anxiety revealed that state anxiety predicts systolic (SBP) and diastolic blood pressure DBP response to CP and AR (P≤0.02). Interestingly, state anxiety predicted heart rate changes only to CP (P<0.01;P=0.3for AR). Although trait anxiety was associated with SBP response to AR and not CP, it was not a significant predictor of reactivity in our models. We conclude that anxiety levels may contribute to the variable blood pressure response to acute stressors and, therefore, should be assessed when performing cardiovascular reactivity measures.

Stress system dysfunction revealed by integrating reactivity of stress pathways to psychological stress in lean and overweight/obese men

2021 ◽  
Author(s):  
Sisitha Udara Jayasinghe ◽  
Sarah Janet Hall ◽  
Susan Jane Torres ◽  
Anne Isabella Turner
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Psychological Stress ◽  
Hpa Axis ◽  
Social Stress ◽  
Blood Pressure Response ◽  
Stress Test ◽  
Trier Social Stress Test ◽  
Stress System

While the patterns of response within the sympatho-adrenal medullary (SAM) system and hypothalamo-pituitary adrenal (HPA) axis are interesting and important in their own accord, the overall response to acute psychological stress involves reactivity of both pathways We tested the hypothesis that consideration of the integrated response of these pathways may reveal dysregulation of the stress systems that is not evident when considering either system alone. Age matched lean and overweight/obese men were subjected to a Trier Social Stress Test and reactivity of the SAM system (salivary alpha amylase, systolic blood pressure, diastolic blood pressure and heart rate) and the HPA axis (salivary cortisol) were measured. Relative reactivity of SAM system and HPA axis was calculated as the ratio between the measures from each pathway. While analysis of reactivity of individual stress pathways showed no evidence of dysfunction in overweight/obese compared with lean men, analysis of HPA/SAM reactivity revealed significantly lower cortisol over systolic blood pressure (CoSBP) and cortisol over diastolic blood pressure (CoDBP) reactivity in overweight/obese compared with lean men. Other measures of HPA/SAM reactivity and all measures of SAM/HPA reactivity were unaltered in overweight/obese compared with lean men. These findings suggest that the cortisol response per unit of blood pressure response is blunted in men with elevated adiposity. Further, these findings support a notion of a coordinated overall approach to activation of the stress pathways with the degree of activation in one pathway being related to the degree of activation of the other.

Abstract 101: Tissue-specific Deletion of Collectrin in the Proximal Tubular Epithelium Increases Arterial Pressure and Augments Salt-sensitivity

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Sylvia Cechova ◽  
Pei-Lun Chu ◽  
Joseph C Gigliotti ◽  
Fan Chan ◽  
Thu H Le
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Collecting Duct ◽  
Critical Role ◽  
Specific Effect ◽  
Salt Sensitivity ◽  
Kidney Cortex ◽  
Mrna Levels ◽  
Proximal Tubular

Background: Collectrin ( Tmem27 ) is a key regulator of blood pressure (BP) and modulator of the bioavailability of nitric oxide (NO) and superoxide. It is highly expressed in the kidney in the proximal tubule (PT), collecting duct, and throughout the vascular endothelium. We reported that collectrin plays a critical role as a chaperone for the reabsorption of all amino acids (AAs) in the PT, and for the uptake of the cationic AA L-arginine (L-Arg) in endothelial cells. Global collectrin knockout ( Tmem27 Y/- ) mice display baseline hypertension (HTN), augmented salt-sensitive hypertension (SSH), and decreased renal blood flow. Objective and Methods: To determine the PT-specific effect of collectrin on BP homeostasis and salt sensitivity, we used the Cre -loxP approach and PEPCK-Cre to generate a mouse line lacking collectrin specifically in the PT-- PEPCK-Cre + Tmem27 Y/Flox mice. PEPCK-Cre - Tmem27 Y/Flox mice were used as control. Radiotelemetry was used to measure BP for 2 weeks at baseline and 2 weeks on high salt diet (HSD). Renal blood flow at baseline and on HSD was measured using contrast enhanced ultrasound in the same mice. Results: Successful deletion of collectrin in the PT was confirmed by assessing mRNA levels using real-time RT-PCR, immunohistochemistry staining of renal tissues using anti-collectrin antibody, and quantitation of protein from kidney cortex by Western analysis. Compared to control PEPCK-Cre - Tmem27 Y/Flox mice (n=6), PEPCK-Cre + Tmem27 Y/Flox mice (n=6) displayed significantly higher systolic BP (SBP) at baseline (120.0 ± 2.5 vs 131.6 ± 2.9 mm Hg; p = 0.014) and after HSD (135.3 ± 2.6 vs 151.5 ± 5.2 mm Hg; p = 0.019). Renal blood flow was not different between groups, at baseline nor after HSD. Conclusion: Collectrin in the PT plays an important role in blood pressure homeostasis and response to sodium intake, independent of renal blood flow. Increasing proximal tubular collectrin activity may be a novel therapeutic strategy for the treatment of hypertension and salt-sensitivity.

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