Variability in Behavioral Phenotypes after Forced Swimming-Induced Stress in Rats Is Associated with Expression of the Glucocorticoid Receptor, Nurr1, and IL-1β in the Hippocampus

Individual differences in coping with stress may determine either a vulnerable or resilient phenotype. Therefore, it is important to better understand the biology underlying the behavioral phenotype. We assessed whether individual behavioral phenotype to acute stress is related with the hippocampal expression of glucocorticoid receptor (GR), Nurr1, interleukin-1 beta (IL-1β) or brain-derived neurotrophic factor (BDNF). Wistar male rats were exposed to forced swimming for 15 min and sacrificed at different times. Behavioral response was analyzed, and it was compared with the gene and protein expression of GR, Nurr1, IL-1β and BDNF in the hippocampus for each time point. Behavioral phenotyping showed a group with high immobility (vulnerable) while another had low immobility (resilient). No significant differences were found in the Nurr1, IL-1β and BDNF mRNA levels between resilient and vulnerable rats at different recovery times except for Nr3c1 (gene for GR). However, exposure to stress caused significantly higher levels of GR, Nurr1 and IL-1β proteins of vulnerable compared to resilient rats. This variability of behavioral phenotypes is associated with a differential molecular response to stress that involves GR, Nurr1, and IL-1β as mediators in coping with stress. This contributes to identifying biomarkers of susceptibility to stress.

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Influence of Dehydration on the Expression of Neuropeptide Y Y1 Receptors in Hypothalamic Magnocellular Neurons

Endocrinology ◽

10.1210/en.2006-0377 ◽

2006 ◽

Vol 147 (9) ◽

pp. 4122-4131 ◽

Cited By ~ 13

Author(s):

Janice H. Urban ◽

Randy J. Leitermann ◽

M. Regina DeJoseph ◽

Suwit J. Somponpun ◽

Michael L. Wolak ◽

...

Keyword(s):

Neuropeptide Y ◽

Male Rats ◽

Mrna Levels ◽

Neural Signals ◽

Salt Loading ◽

Paraventricular Nuclei ◽

Gene And Protein Expression ◽

Body Weights ◽

Cell Groups ◽

Y1 Receptors

Regulation of vasopressin (VP) and oxytocin (OT) secretion involves integration of neural signals from hypothalamic osmoreceptors, ascending catecholaminergic and peptidergic cell groups in the brain stem, and local and autoregulatory afferents. Neuropeptide Y (NPY) is one factor that stimulates the release of VP and OT from the supraoptic (SON) and paraventricular nuclei of the hypothalamus via activation of Y1 receptors (Y1R). The current studies were designed to assess the regulation and distribution of NPY Y1R expression in the SON of male rats that were either given 2% NaCl drinking water (24–72 h) or water deprived (48 h). Subjecting male rats to these conditions resulted in significant increases in both the number of cells expressing Y1R immunoreactivity (ir) and the amount of Y1R protein per cell within the SON. Y1R immunoreactivity was increased in the magnocellular but not medial parvocellular paraventricular nuclei, and Y1R mRNA levels were increased in the SON of salt-loaded rats. Subpopulations of both VP and OT cells in the hypothalamus express Y1R immunoreactivity and a greater percentage of VP-ir cells express Y1R after salt loading. To control for potential effects of dehydration-induced anorexia, a group of euhydrate animals was pair fed with animals consuming 2% NaCl. No detectable change in Y1R expression was observed in the SON of pair-fed animals, even though body weights were significantly lower than controls. These data demonstrate that NPY Y1R gene and protein expression are increased in the SON of salt-loaded and water-deprived animals and provide a mechanism whereby NPY can support VP/OT release during prolonged challenges to fluid homeostasis.

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Vasopressin Administration into the Paraventricular Nucleus Normalizes Plasma Oxytocin and Corticosterone Levels in Brattleboro Rats

Endocrinology ◽

10.1210/en.2008-1007 ◽

2009 ◽

Vol 150 (6) ◽

pp. 2791-2798 ◽

Cited By ~ 21

Author(s):

Dóra Zelena ◽

Kristina Langnaese ◽

Ágnes Domokos ◽

Ottó Pintér ◽

Rainer Landgraf ◽

...

Keyword(s):

Paraventricular Nucleus ◽

Stress Responses ◽

Extracellular Fluid ◽

Plasma Corticosterone ◽

Forced Swimming ◽

Male Rats ◽

Congenital Absence ◽

Mrna Levels ◽

Intact Control ◽

The Impact

Adult male rats of the Brattleboro strain were used to investigate the impact of the congenital absence of vasopressin on plasma adrenocorticotropin, corticosterone, and oxytocin concentrations as well as the release pattern of oxytocin within the hypothalamic paraventricular nucleus (PVN), in response to a 10-min forced swimming session. Measurement of adrenocorticotropin in plasma samples collected via chronically implanted jugular venous catheters revealed virtually identical stress responses for vasopressin-lacking Brattleboro (KO) and intact control animals. In contrast, plasma corticosterone and oxytocin levels were found to be significantly elevated 105 min after onset of the stressor in KO animals only. Microdialysis samples collected from the extracellular fluid of the PVN showed significantly higher levels of oxytocin both under basal conditions and in response to stressor exposure in KO vs. intact control animals accompanied by elevated oxytocin mRNA levels in the PVN of KO rats. These findings suggest that the increased oxytocin levels in the PVN caused by the congenital absence of vasopressin may contribute to normal adrenocorticotropin stress responses in KO animals. However, whereas the stressor-induced elevation of plasma oxytocin in KO rats may be responsible for their maintained corticosterone levels, oxytocin seems unable to fully compensate for the lack of vasopressin. This hypothesis was tested by retrodialyzing synthetic vasopressin into the PVN area concomitantly with blood sampling in KO animals. Indeed, this treatment normalized plasma oxytocin and corticosterone levels 105 min after forced swimming. Thus, endogenous vasopressin released within the PVN is likely to act as a paracrine signal to facilitate the return of plasma oxytocin and corticosterone to basal levels after acute stressor exposure.

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Glutamine synthetase expression in muscle is regulated by transcriptional and posttranscriptional mechanisms

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.276.6.e1136 ◽

1999 ◽

Vol 276 (6) ◽

pp. E1136-E1145 ◽

Cited By ~ 6

Author(s):

Brian I. Labow ◽

Wiley W. Souba ◽

Steve F. Abcouwer

Keyword(s):

Glutamine Synthetase ◽

Chronic Stress ◽

Acute Stress ◽

Physiological Stress ◽

Male Rats ◽

Methionine Sulfoximine ◽

Mrna Levels ◽

Protein Levels ◽

Acute And Chronic Stress ◽

Gs Protein

Skeletal muscle exports glutamine (Gln) and increases the expression of the enzyme glutamine synthetase (GS) in response to physiological stress. Acute stress or direct glucocorticoid administration raises muscle GS mRNA levels dramatically without a parallel increase in GS protein levels. In the lung, this discrepancy is caused by feedback destabilization of the GS protein by its product Gln. It was hypothesized that muscle GS protein levels increase during stress only when the intracellular Gln pool has been depleted. Adult male rats were injected with the glucocorticoid hormone dexamethasone (DEX) to mimic the acute stress response and with the GS inhibitor methionine sulfoximine (MSO) to deplete muscle Gln stores. DEX increased GS mRNA levels by 2.8-fold but increased GS protein levels by an average of only 40%. MSO diminished muscle GLN levels by 68% and caused GS protein levels to rise in accordance with GS mRNA. Chronic stress was mimicked using 6 days of MSO treatment, which produced anorexia, 23% loss of body weight, and 64% decrease in muscle Gln levels, as well as pronounced increases in both muscle GS mRNA (26-fold) and protein levels (35-fold) without elevation of plasma glucocorticoid levels. Calorie-restricted pair-fed animals exhibited lesser increases in muscle GS mRNA (8-fold) and protein levels (5-fold) without a decline in muscle Gln content. Thus regulation of GS expression in both acute and chronic stress involved both transcriptional and posttranscriptional mechanisms, perhaps affected by muscle Gln content.

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The effect of dexamethasone on mucosal immunity of uterine tissue during pregnancy in rat

Mansoura Veterinary Medical Journal ◽

10.35943/mvmj.2019.01.1013 ◽

2019 ◽

Vol 20 (1) ◽

pp. 75-84

Keyword(s):

Early Pregnancy ◽

Histopathological Examination ◽

Early Period ◽

Interleukin 10 ◽

Treated Group ◽

Female Rats ◽

Male Rats ◽

Mrna Levels ◽

Uterine Tissue ◽

Leukocytic Infiltration

Disturbances in early pregnancy immunity affect embryo development, endometrial receptivity, placental development, fetal growth and lead to subfertility, dexamethasone is a synthetic glucocorticoid used for treatment of various complications. Immune cells and cytokines were examined during the early pregnancy in twenty-four female rats and six male rats for mating. Rats were grouped into two group control and dexamethasone treated by a dose of 50µgm/kgm body weight daily starting from one week before mating and persisted for one week after pregnancy. Blood samples were collected from each rat at 5hrs and at 1,3,7 day of pregnancy. Extracted RNA was subjected to real time PCR to determine mRNA levels for immune related genes interleukin1a(IL1A) and interleukin 10(IL10). Histopathological examination was done to uterus in order to detect leukocyte infiltration in uterine tissue. Results showed that significant increase in white blood cell count mainly eosinophil at 5hrs and lymphocyte at three and seven day of pregnancy of dexamethasone treated group. Moreover, TNF, C-reactive protein and progesterone were increased mainly at seven day of pregnancy of dexamethasone treated group. Similarly, interleukin 1alpha and interleukin 10 significantly increased at 5hrs and one day of pregnancy of dexamethasone treated group. In contrast, serum levels of total antioxidant capacity and estrogen were decreased significantly at 5hrs and seven day in dexamethasone treated group. Histopathological examination of uterus revealed leukocytic infiltration especially neutrophil and few eosinophils at five hours and one day of gestation then eosinophil become absent at 3day and seven day of dexamethasone group. Epithelial height and uterine gland diameter significantly increased at 5hrs, three day and seven days of gestation of dexamethasone treated group. The present investigation demonstrated that using of dexamethasone by dose of 50µgm/kgm during early pregnancy had a conflicting impact on some immune cytokines and parameters and may reflect a harmful response of immune system toward early period of pregnancy

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Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

Biological Research ◽

10.1186/s40659-021-00328-4 ◽

2021 ◽

Vol 54 (1) ◽

Author(s):

Mayarling Francisca Troncoso ◽

Mario Pavez ◽

Carlos Wilson ◽

Daniel Lagos ◽

Javier Duran ◽

...

Keyword(s):

Glucose Metabolism ◽

Cardiac Hypertrophy ◽

Glucose Uptake ◽

Male Rats ◽

Cardiomyocyte Hypertrophy ◽

Mrna Levels ◽

Elevated Glucose ◽

Amp Activated Protein Kinase ◽

Cultured Cardiomyocytes

Abstract Background Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake—via AMP-activated protein kinase (AMPK)—after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). Methods Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). Results Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels. Conclusion These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

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Association of Behavioral Phenotypes With Changes in Sleep During a Workplace Wellness Program

American Journal of Health Promotion ◽

10.1177/08901171211015089 ◽

2021 ◽

pp. 089011712110150

Author(s):

Kimberly J. Waddell ◽

Sujatha Changolkar ◽

Gregory Szwartz ◽

Sarah Godby ◽

Mitesh S. Patel

Keyword(s):

Physical Activity ◽

Sleep Duration ◽

Physical Activity Intervention ◽

Secondary Analysis ◽

The United States ◽

Behavioral Phenotype ◽

Workplace Wellness ◽

Wellness Program ◽

Behavioral Phenotypes ◽

Physically Active

Purpose: Examine changes in sleep duration by 3 behavioral phenotypes during a workplace wellness program with overweight and obese adults. Design: Secondary analysis of a randomized clinical trial Setting: Remotely monitored intervention conducted across the United States Subjects: 553 participants with a body mass index ≥25 Intervention: Participants were randomized to 1 of 4 study arms: control, gamification with support, gamification with collaboration, and gamification with competition to increase their physical activity. All participants were issued a wrist-worn wearable device to record their daily physical activity and sleep duration. Measures: The primary outcome was change in daily sleep duration from baseline during the 24 week intervention and follow-up period by study arm within behavioral phenotype class. Analysis: Linear mixed effects regression. Results: Participants who had a phenotype of less physically active and less social at baseline, in the gamification with collaboration arm, significantly increased their sleep duration during the intervention period (30.2 minutes [95% CI 6.9, 53.5], P = 0.01), compared to the control arm. There were no changes in sleep duration among participants who were more extroverted and motivated or participants who were less motivated and at-risk. Conclusions: Changes in sleep during a physical activity intervention varied by behavioral phenotype. Behavioral phenotypes may help to precisely identify who is likely to improve sleep duration during a physical activity intervention.

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Thyroid-stimulating hormone decreases the risk of osteoporosis by regulating osteoblast proliferation and differentiation

BMC Endocrine Disorders ◽

10.1186/s12902-021-00715-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Tuo Deng ◽

Wenwen Zhang ◽

Yanling Zhang ◽

Mengqi Zhang ◽

Zhikun Huan ◽

...

Keyword(s):

Thyroid Function ◽

Thyroid Stimulating Hormone ◽

Mrna Levels ◽

Dependent Manner ◽

Osteoblast Proliferation ◽

Normal Thyroid ◽

Normal Thyroid Function ◽

Gene And Protein Expression ◽

Proliferation And Differentiation ◽

Stimulating Hormone

Abstract Background As the incidence of secretory osteoporosis has increased, bone loss, osteoporosis and their relationships with thyroid-stimulating hormone (TSH) have received increased attention. In this study, the role of TSH in bone metabolism and its possible underlying mechanisms were investigated. Methods We analyzed the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH and the bone mineral density (BMD) levels of 114 men with normal thyroid function. In addition, osteoblasts from rat calvarial samples were treated with different doses of TSH for different lengths of time. The related gene and protein expression levels were investigated. Results A comparison of the BMD between the high-level and low-level serum TSH groups showed that the TSH serum concentration was positively correlated with BMD. TSH at concentrations of 10 mU/mL and 100 mU/mL significantly increased the mRNA levels of ALP, COI1 and Runx2 compared with those of the control (P < 0.05, P < 0.01). Bone morphogenetic protein (BMP)2 activity was enhanced with both increased TSH concentration and increased time. The protein levels of Runx2 and osterix were increased in a dose-dependent manner. Conclusions The circulating concentrations of TSH and BMD were positively correlated with normal thyroid function in males. TSH promoted osteoblast proliferation and differentiation in rat primary osteoblasts.

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Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyz050 ◽

2019 ◽

Vol 22 (11) ◽

pp. 710-723 ◽

Cited By ~ 8

Author(s):

Atul P Daiwile ◽

Subramaniam Jayanthi ◽

Bruce Ladenheim ◽

Michael T McCoy ◽

Christie Brannock ◽

...

Keyword(s):

Sex Differences ◽

Nucleus Accumbens ◽

Fixed Ratio ◽

Female Rats ◽

Male Rats ◽

Mrna Levels ◽

Self Administration ◽

Male And Female ◽

Orexin Receptors ◽

Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

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Effect of different types of stressors on peptide messenger ribonucleic acids in the hypothalamic paraventricular nucleus

Acta Endocrinologica ◽

10.1530/acta.0.1280485 ◽

1993 ◽

Vol 128 (6) ◽

pp. 485-492 ◽

Cited By ~ 42

Author(s):

Sandra Ceccatelli ◽

Catello Orazzo

Keyword(s):

Paraventricular Nucleus ◽

Immobilization Stress ◽

Thyrotropin Releasing Hormone ◽

Hypothalamic Paraventricular Nucleus ◽

Male Rats ◽

Mrna Levels ◽

Corticotropin Releasing Hormone ◽

Ribonucleic Acids ◽

Releasing Hormone ◽

Different Types

Using in situ hybridization we have studied the effects of different types of stressors, such as ether, immobilization, cold and swimming, on the expression of several peptide messenger ribonucleic acids (mRNAs) in the hypothalamic paraventricular nucleus of adult male rats. Paraventricular nucleus sections were hybridized using synthetic oligonucleotide probes complementary to mRNA for corticotropin-releasing hormone, neurotensin, enkephalin and thyrotropin-releasing hormone. A clear upregulation of neurotensin mRNA was seen after ether and, to a lesser extent, after immobilization stress, whereas after the two other stressors neurotensin mRNA was undetectable, as in control rats. An increase in enkephalin mRNA was observed in a selective region of the dorsal part of the medioparvocellular subdivision of the paraventricular nucleus only after ether and immobilization stress. No significant changes were seen in corticotropin-releasing hormone and thyrotropin-releasing hormone mRNA levels in any of the experimental paradigms. The present results show selective changes for various peptide mRNAs in the paraventricular nucleus after various types of stress. Significant effects could be demonstrated only on neurotensin and enkephalin mRNA after ether and immobilization stress. This suggests that adaptive changes in the rate of synthesis, processing and transport of the peptide may develop over a longer period of time.

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