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2.
Sci Rep ; 13(1): 38, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593340

RESUMO

Robustness can refer to an animal's ability to overcome perturbations. Intense selection for production traits in livestock has resulted in reduced robustness which has negative implications for livability as well as production. There is increasing emphasis on improving robustness through poultry breeding, which may involve identifying novel phenotypes that could be used in selection strategies. The hypothalamic-pituitary-adrenal (HPA) axis and associated hormones (e.g., corticosterone) participate in many metabolic processes that are related to robustness. Corticosterone can be measured non-invasively in feathers (FCORT) and reflects the average HPA axis activity over the feather growing period, however measurement is expensive and time consuming. Fault bars are visible feather deformities that may be related to HPA axis activity and may be a more feasible indicator trait. In this study, we estimated variance components for FCORT and fault bars in a population of purebred turkeys as well as their genetic and partial phenotypic correlations with other economically relevant traits including growth and efficiency, carcass yield, and meat quality. The estimated heritability for FCORT was 0.21 ± 0.07 and for the fault bar traits (presence, incidence, severity, and index) estimates ranged from 0.09 to 0.24. The genetic correlation of FCORT with breast weight, breast meat yield, fillet weight, and ultimate pH were estimated at -0.34 ± 0.21, -0.45 ± 0.23, -0.33 ± 0.24, and 0.32 ± 0.24, respectively. The phenotypic correlations of FCORT with breast weight, breast meat yield, fillet weight, drum weight, and walking ability were -0.16, -0.23, -0.18, 0.17, and 0.21, respectively. Some fault bar traits showed similar genetic correlations with breast weight, breast meat yield, and walking ability but the magnitude was lower than those with FCORT. While the dataset is limited and results should be interpreted with caution, this study indicates that selection for traits related to HPA axis activity is possible in domestic turkeys. Further research should focus on investigating the association of these traits with other robustness-related traits and how to potentially implement these traits in turkey breeding.


Assuntos
Plumas , Perus , Animais , Perus/genética , Corticosterona , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Fenótipo
3.
Commun Biol ; 6(1): 81, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681730

RESUMO

Peripheral clocks function to regulate each organ and are synchronized though various molecular and behavioral signals. However, signals that entrain the bladder clock remain elusive. Here, we show that glucocorticoids are a key cue for the bladder clock in vitro and in vivo. A pBmal1-dLuc human urothelial cell-line showed significant shifts in gene expression after cortisol treatment. In vivo, rhythmic bladder clock gene expression was unchanged by bilateral adrenalectomy but shifted 4 h forward by corticosterone administration at the inactive phase. Moreover, the bladder clock shifted 8-12 h in mice that underwent both bilateral adrenalectomy and corticosterone administration at the inactive phase. These mice showed decreases in the diurnal rhythm of volume voided per micturition, while maintaining diurnal activity rhythms. These results indicate that the diurnal rhythm of glucocorticoid signaling is a zeitgeber that overcomes other bladder clock entrainment factors and coordinates the diurnal rhythm of volume voided per micturition.


Assuntos
Corticosterona , Glucocorticoides , Camundongos , Humanos , Animais , Glucocorticoides/farmacologia , Corticosterona/metabolismo , Micção , Bexiga Urinária , Ritmo Circadiano/fisiologia
4.
PLoS One ; 18(1): e0279209, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36662804

RESUMO

Circadian, metabolic, and reproductive systems are inter-regulated. Excessive fatness and circadian disruption alter normal physiology and the endocrine milieu, including cortisol, the primary stress hormone. Our aim was to determine the effect feeding a high fat diet to female ICR mice had on diurnal feeding pattern, weight gain, body composition, hair corticosterone levels and circadian patterns of fecal corticosterone. Prepubertal (~35d of age) ICR mice were assigned to control (CON; 10% fat) or high fat (HF; 60% fat) diet and fed for 4 wk to achieve obesity under 12h light and 12h of dark. Feed intake was measured twice daily to determine diurnal intake. Mice were weighed weekly. After 4 wk on diets hair was collected to measure corticosterone, crown-rump length was measured to calculate body mass index (BMI), and body composition was measured with EchoMRI to determine percent fat. HF mice weighed more (P<0.05) after week two, BMI and percent body fat was greater (P<0.05) in HF than CON at the end of wk 4. HF mice consumed more during the day (P<0.05) than CON mice after 1 week on diets. Hair corticosterone was higher in HF mice than in CON (P<0.05). Fecal circadian sampling over 48hr demonstrated that HF mice had elevated basal corticosterone, attenuated circadian rhythms, and a shift in amplitude. High fat feeding for diet induced obesity alters circadian eating pattern and corticosterone rhythms, indicating a need to consider the impact of circadian system disruption on reproductive competence.


Assuntos
Corticosterona , Dieta Hiperlipídica , Feminino , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos ICR , Obesidade/etiologia , Obesidade/metabolismo , Comportamento Alimentar/fisiologia , Ingestão de Alimentos/fisiologia , Dieta , Ritmo Circadiano/fisiologia
5.
J Tradit Chin Med ; 43(1): 113-123, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36640002

RESUMO

OBJECTIVE: To investigated the effects of suspended moxibustion stimulating Shenshu (BL23) and Guanyuan (CV4) acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney- deficiency symptom pattern (KYDS). METHODS: Sixty male Sprague Dawley rats were randomly divided into a control group ( 12) and an experimental group ( 48). Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model. The 48 rats successfully modeled were then randomly divided into a model group (model, 12), a carbenoxolone intraperitoneal injection group (CBX, 12), a moxibustion group (moxi, 12), and a moxi + CBX group ( 12). In the moxi, the Shenshu (BL23) and Guanyuan (CV 4) acupoints were treated with moxibustion for 14 d. After treatment, measures were taken of serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), and corticotropin-releasing hormone (CRH). The expression of mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs), 11beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), CRH, and ACTH in the rats' amygdala, hypothalamus, or pituitary (as appropriate) was detected. Data were analyzed using one-way analysis of variance. RESULTS: Compared with those of the control group, the serum levels of CRH, ACTH, and CORT; the mRNA and protein expressions of MR, GR, and 11ß-HSD1 in the amygdala; the mRNA and protein expressions of 11ß-HSD1 in the hypothalamus; the CRH mRNA expression in the amygdala and hypothalamus; and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased (0.05 or 0.01). After treatment with moxibustion, all the aforementioned observation indices except for 11ß-HSD1 mRNA expression were ameliorated compared with those in the model group (0.05 or 0.01). CONCLUSIONS: Suspended moxibustion can effectively improve the serum levels of ACTH, CRH, and CORT and can up-regulate the mRNA and protein expressions of MR, GR, 11ß-HSD1, CRH, and ACTH in the amygdala and hypothalamus of KYDS rats. This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.


Assuntos
Hidrocortisona , Moxibustão , Ratos , Masculino , Animais , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Ratos Sprague-Dawley , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/farmacologia , Sistema Hipófise-Suprarrenal/metabolismo , Hormônio Liberador da Corticotropina/genética , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Corticosterona/metabolismo , Tonsila do Cerebelo/metabolismo , RNA Mensageiro/metabolismo , Rim/metabolismo
6.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674444

RESUMO

Steroid hormones are synthesized through enzymatic reactions using cholesterol as the substrate. In steroidogenic cells, the required cholesterol for steroidogenesis can be obtained from blood circulation or synthesized de novo from acetate. One of the key enzymes that control cholesterol synthesis is 24-dehydrocholesterol reductase (encoded by DHCR24). In humans and rats, DHCR24 is highly expressed in the adrenal gland, especially in the zona fasciculata. We recently reported that DHCR24 was expressed in the mouse adrenal gland's inner cortex and also found that thyroid hormone treatment significantly upregulated the expression of Dhcr24 in the mouse adrenal gland. In the present study, we showed the cellular expression of DHCR24 in mouse adrenal glands in early postnatal stages. We found that the expression pattern of DHCR24 was similar to the X-zone marker gene 20αHSD in most developmental stages. This finding indicates that most steroidogenic adrenocortical cells in the mouse adrenal gland do not synthesize cholesterol locally. Unlike the 20αHSD-positive X-zone regresses during pregnancy, some DHCR24-positive cells remain present in parous females. Conditional knockout mice showed that the removal of Dhcr24 in steroidogenic cells did not affect the overall development of the adrenal gland or the secretion of corticosterone under acute stress. Whether DHCR24 plays a role in conditions where a continuous high amount of corticosterone production is needed requires further investigation.


Assuntos
Corticosterona , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Humanos , Camundongos , Feminino , Ratos , Animais , Corticosterona/metabolismo , Glândulas Suprarrenais/metabolismo , Zona Fasciculada/metabolismo , Colesterol/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
7.
Poult Sci ; 102(2): 102379, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608454

RESUMO

Stress can suppress reproduction capacity in either wild or domestic animals, but the exact mechanism behind it, especially in terms of steroidogenesis, remains under-investigated so far. Considering the important roles of progesterone in avian breeding, we investigated the modulation of corticosterone on progesterone production in cultured granulosa cells of chicken follicles at different developmental stages. Using enzyme immunoassays, our study showed that corticosterone could only inhibit progesterone synthesis in granulosa cells from F5-6, F4, and F3 follicles, but not F2 and F1 follicles. Coincidentally, both quantitative real-time PCR and western blotting revealed that corticosterone could downregulate steroidogenic acute regulatory protein (StAR) expression, suggesting the importance of StAR in corticosterone-related actions. Using the dual-luciferase reporter system, we found that corticosterone can potentially enhance, rather than inhibit, the activity of StAR promoter. Of note, combining high-throughput transcriptomic analysis and quantitative real-time PCR, phosphodiesterase 10A (PDE10A), protein kinase cAMP-dependent type II regulatory subunit alpha (PRKAR2A) and cAMP responsive element modulator (CREM) were identified to exhibit the differential expression patterns consistent with cAMP blocking in granulosa cells from F5-6, F4, and F3, but not F2 and F1 follicles. Afterward, the expression profiles of these genes in granulosa cells of distinct developmental-stage follicles were examined by quantitative real-time PCR, in which all of them expressed correspondingly with progesterone levels of granulosa cells during development. Collectively, these findings indicate that corticosterone can stage-dependently inhibit progesterone production in granulosa cells of chicken preovulatory follicles, through impeding cAMP-induced StAR activity presumptively.


Assuntos
Galinhas , Progesterona , Feminino , Animais , Progesterona/metabolismo , Galinhas/metabolismo , Corticosterona/metabolismo , Células da Granulosa/metabolismo , Células Cultivadas
8.
Poult Sci ; 102(2): 102390, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608455

RESUMO

Prenatal stress may evoke considerable physiological consequences on the developing poultry embryos and neonates. The present study aimed to determine prenatal auditory stimulation effects on serum levels of ceruloplasmin (CPN), alpha-1-acid glycoprotein (AGP), corticosterone (CORT), and heat shock protein 70 (Hsp70) regulations in developing chicken embryos and newly hatched chicks. Hatching eggs were subjected to the following auditory treatments; 1) control (no additional sound treatment other than the background sound of the incubator's compressors at 40 dB), 2) noise exposure (eggs were exposed to pre-recorded traffic noise at 90 dB) (NOISE), and 3) music exposure (eggs were exposed to Mozart's Sonata for Two Pianos in D Major, K 488 at 90 dB) (MUSIC). The NOISE and MUSIC treatments were for 20 min/h for 24 h (a total of 8 h/d), starting from embryonic days (ED) 12 to hatching. The MUSIC (1.37 ± 0.1 ng/mL) and NOISE (1.49 ± 0.2 ng/mL) treatments significantly elevated CPN at ED 15 compared to the Control (0.82 ± 0.04 ng/mL) group and post-hatch day 1 (Control, 1.86 ± 0.2 ng/mL; MUSIC, 2.84 ± 0.4 ng/mL; NOISE, 3.04 ± 0.3 ng/mL), AGP at ED 15 (Control, 39.1 ± 7.1 mg/mL; MUSIC, 85.5 ± 12.9 mg/mL; NOISE, 85.4 ± 15.1 mg/mL) and post-hatch day 1 (Control, 20.4 ± 2.2 mg/mL; MUSIC, 30.5 ± 4.7 mg/mL; NOISE, 30.3 ± 1.4 mg/mL). CORT significantly increased at ED 15 in both MUSIC (9.024 ± 1.4 ng/mL) and NOISE (12.15 ± 1.6 ng/mL) compared to the Control (4.39 ± 0.7 ng/mL) group. On the other hand, MUSIC exposed embryos had significantly higher Hsp70 expression than their Control and NOISE counterparts at ED 18 (Control, 12.9 ± 1.2 ng/mL; MUSIC, 129.6 ± 26.4 ng/mL; NOISE, 13.3 ± 2.3 ng/mL) and post-hatch day 1 (Control, 15.2 ± 1.7 ng/mL; MUSIC, 195.5 ± 68.5 ng/mL; NOISE, 13.2 ± 2.7 ng/mL). In conclusion, developing chicken embryos respond to auditory stimulation by altering CPN, AGP, CORT, and Hsp70. The alterations of these analytes could be important in developing embryos and newly hatched chicks to cope with stress attributed to auditory stimulation.


Assuntos
Galinhas , Óvulo , Embrião de Galinha , Animais , Galinhas/fisiologia , Estimulação Acústica/veterinária , Óvulo/metabolismo , Ruído/efeitos adversos , Vitaminas , Estresse Fisiológico , Corticosterona , Proteínas de Choque Térmico HSP70/metabolismo
9.
J Neuroendocrinol ; 35(1): e13231, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36683309

RESUMO

Prenatal stress (PS) causes anxiety in mothers and their offspring and chewing is a commonly observed behavior during maternal stress. Prolactin (PRL) is an anti-anxiety factor that suppresses the hypothalamic-pituitary-adrenal axis. Here, we studied the roles of PRL, corticosterone (CORT), and their receptors in PS-induced anxiety-like behavior in dams and their offspring. We further investigated whether chewing during maternal stress could prevent PS-induced harmful consequences. Pregnant rats were randomly divided into PS, PS + chewing, and control groups. Anxiety-like behaviors of dams and their adolescent offspring were assessed using the open field test and elevated plus maze. Serum levels of PRL and CORT were measured by ELISA. Expression of mRNA and protein of PRLR and glucocorticoid receptor (GR) in the prefrontal cortex (PFC) were evaluated by qRT-PCR and western blotting, respectively. Compared to the control rats, dams and their female offspring, but not male offspring, in the PS group showed increased anxiety-like behaviors. The PS-affected rats had a lower serum PRL level and increased PRLR expression in the PFC. In contrast, these rats had a higher serum CORT level and decreased GR expression in the PFC. Chewing ameliorated anxiety-like behaviors and counteracted stress-induced changes in serum PRL and CORT, as well as the expression of their receptors in the PFC. Conclusion: PS-induced anxiety-like behavior is associated with changes in the serum levels of PRL and CORT and expression of their receptors in the PFC. Moreover, chewing blunts the hormonal and receptor changes and may serve as an effective stress-coping method for preventing PS-induced anxiety-like behavior.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Receptores de Glucocorticoides , Gravidez , Ratos , Animais , Feminino , Humanos , Receptores de Glucocorticoides/metabolismo , Ratos Sprague-Dawley , Prolactina/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Corticosterona , Córtex Pré-Frontal/metabolismo , Estresse Psicológico/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo
10.
Neurosci Lett ; 792: 136959, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36370954

RESUMO

Sleep disruption (SD) promotes stress which may mediate the effect of SD induced by noise on bodyweight gain and food intake. We determined if the change in bodyweight during SD caused by noise was driven by stress (assessed by corticosterone) and whether the effects of noise on SD, stress and bodyweight were specific to the method of SD or a consequence of SD per se. We isolated stress from SD due to noise by exposing rats to noise during the darkphase to test whether darkphase noise stimulated weight gain, stress and food intake. Male Sprague-Dawley rats slept undisturbed, were exposed to noise during both circadian phases (lightphase vs darkphase) and lightphase gentle handling. Bodyweight, food intake, physical activity, vigilance states, and plasma corticosterone were determined. Darkphase noise did not affect vigilance states. Unlike lightphase noise, darkphase noise and lightphase gentle handling did not stimulate weight gain or food intake. Only gentle handling significantly increased corticosterone levels. Noise during the lightphase increasesed weight gain and food intake by causing SD and these effects were not driven by stress as assessed by corticosterone. These results may have significant implications for developing translational models of insomnia-induced obesity in humans.


Assuntos
Corticosterona , Distúrbios do Início e da Manutenção do Sono , Humanos , Ratos , Animais , Masculino , Privação do Sono , Ratos Sprague-Dawley , Sono , Aumento de Peso , Peso Corporal
11.
Psychoneuroendocrinology ; 147: 105953, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36334546

RESUMO

Chronic stress is a known risk factor for the development of major depression (MDD) and is commonly used to induce a depression-like phenotype in rodents. Similar phenotypic effects are also observed in rodents when treated chronically with the stress hormone corticosterone. In this study, we investigated the neuropsychological consequences of chronic corticosterone treatment in male rats using two translational rodent assays of affective bias, the judgement bias task (JBT) and affective bias test (ABT). We also used the reward learning assay (RLA) and sucrose preference test (SPT) to quantify reward-related behaviours. Negative biases in decision-making were observed in the chronic corticosterone-treated group but only when the treatment was given shortly before each behavioural session. The same dose of corticosterone, when given daily after completion of the behavioural session had no effects. Chronic corticosterone treatment did not potentiate negative affective biases in the ABT induced by either an acute pharmacological or stress manipulation but both reward learning and reward sensitivity were blunted. Analysis of the brain tissue from animals receiving chronic corticosterone found reduced hippocampal neurogenesis consistent with previous studies suggesting corticosterone-induced neurotrophic deficits. Taken together, these data suggest chronic corticosterone treatment induces neuropsychological effects related to changes in reward learning, memory and negative biases in decision making, but these decision-making biases depend on whether rewarding outcomes were experienced during the acute effects of the drug. These findings suggest an important interaction between psychological and biological factors resulting in negative biases in decision-making in this model.


Assuntos
Corticosterona , Transtorno Depressivo Maior , Ratos , Masculino , Animais , Corticosterona/farmacologia , Depressão/psicologia , Recompensa , Julgamento
12.
Gen Comp Endocrinol ; 330: 114126, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36122793

RESUMO

Alzheimer's disease (AD) is a progressive, dementing, whole-body disorder that presents with decline in cognitive, behavioral, and emotional functions, as well as endocrine dysregulation. The etiology of AD is not fully understood but stress- and anxiety-related hormones may play a role in its development and trajectory. The glucocorticoid cascade hypothesis posits that levels of glucocorticoids increase with age, leading to dysregulated negative feedback, further elevated glucocorticoids, and resulting neuropathology. We examined the impact of age (from 2 to 10 months) and stressor exposure (predator odor) on hormone levels (corticosterone and ghrelin), anxiety-like behavior (open field and light dark tests), and memory-related behavior (novel object recognition; NOR), and whether these various measures correlated with neuropathology (hippocampus and cortex amyloid beta, Aß) in male and female APPswe/PS1dE9 transgenic and non-transgenic mice. Additionally, we performed exploratory analyses to probe if the open field and light dark test as commonly used tasks to assess anxiety levels were correlated. Consistent with the glucocorticoid cascade hypothesis, baseline corticosterone increased with age. Predator odor exposure elevated corticosterone at each age, but in contrast to the glucocorticoid cascade hypothesis, the magnitude of stressor-induced elevations in corticosterone levels did not increase with age. Overall, transgenic mice had higher post-stressor, but not baseline, corticosterone than non-transgenic mice, and across both genotypes, females consistently had higher (baseline and post-stressor) corticosterone than males. Behavior in the open field test primarily showed decreased locomotion with age, and this was pronounced in transgenic females. Anxiety-like behaviors in the light dark test were exacerbated following predator odor, and female transgenic mice were the most impacted. Compared to transgenic males, transgenic females had higher Aß concentrations and showed more anxiety-like behavior. Performance on the NOR did not differ significantly between genotypes. Lastly, we did not find robust, statistically significant correlations among corticosterone, ghrelin, recognition memory, anxiety-like behaviors, or Aß, suggesting outcomes are not strongly related on the individual level. Our data suggest that despite Aß accumulation in the hippocampus and cortex, male and female APPswePS1dE9 transgenic mice do not differ robustly from their non-transgenic littermates in physiological, endocrine, and behavioral measures at the range of ages studied here.


Assuntos
Doença de Alzheimer , Glucocorticoides , Camundongos , Masculino , Feminino , Animais , Corticosterona , Grelina , Peptídeos beta-Amiloides/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Ansiedade , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Camundongos Transgênicos , Envelhecimento/fisiologia , Estresse Psicológico
13.
Gen Comp Endocrinol ; 330: 114150, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36349607

RESUMO

Among all the regulatory homeostatic networks in vertebrates, the activation of the hypothalamic-pituitaryadrenal axis during the stress response, has gained considerable attention, and the measurement of fecal glucocorticoids (FGC) has become an invaluable tool to assess adrenocortical activity related to stressful events in wild and captive animals. However, the use of FGC requires the validation of measurement techniques and the proper selection of the specific hormone according to the study species. The main objective of this study was to identify the dominant glucocorticoid (GC) hormone in the stress response of black-tailed prairie dogs (Cynomys ludovicianus) in an arid grassland of Chihuahua, Mexico. A capture stress challenge in the field was developed to determine if the levels of glucocorticoids (cortisol and corticosterone) both in serum and fecal samples could be attributed to stress in Cynomys ludovicianus. The samples were analysed with the technique of liquid phase radioimmunoassay , and this study showed that both cortisol and corticosterone are present at measurable levels in serum and fecal samples of black-tailed prairie dogs. We found that both GCs were present in similar concentrations in serum, however, corticosterone concentration in fecal samples was higher than cortisol. Likewise, biochemical validations performed in this study to test the assay reached acceptable levels of reliability. Therefore, we confirm that fecal analysis can be implemented as a method to measure stress responses in wild prairie dogs.


Assuntos
Corticosterona , Glucocorticoides , Animais , Hidrocortisona , México , Reprodutibilidade dos Testes , Sciuridae
14.
Clin Chem Lab Med ; 61(1): 67-77, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36288389

RESUMO

OBJECTIVES: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) panels that include glucocorticoid-related steroids are increasingly used to characterize and diagnose adrenal cortical diseases. Limited information is currently available about reproducibility of these measurements among laboratories. The aim of the study was to compare LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone at eight European centers and assess the performance after unification of calibration. METHODS: Seventy-eight patient samples and commercial calibrators were measured twice by laboratory-specific procedures. Results were obtained according to in-house and external calibration. We evaluated intra-laboratory and inter-laboratory imprecision, regression and agreement against performance specifications derived from 11-deoxycortisol biological variation. RESULTS: Intra-laboratory CVs ranged between 3.3 and 7.7%, 3.3 and 11.8% and 2.7 and 12.8% for corticosterone, 11-deoxycortisol and cortisone, with 1, 4 and 3 laboratories often exceeding the maximum allowable imprecision (MAI), respectively. Median inter-laboratory CVs were 10.0, 10.7 and 6.2%, with 38.5, 50.7 and 2.6% cases exceeding the MAI for corticosterone, 11-deoxycortisol and cortisone, respectively. Median laboratory bias vs. all laboratory-medians ranged from -5.6 to 12.3% for corticosterone, -14.6 to 12.4% for 11-deoxycortisol and -4.0 to 6.5% for cortisone, with few cases exceeding the total allowable error. Modest deviations were found in regression equations among most laboratories. External calibration did not improve 11-deoxycortisol and worsened corticosterone and cortisone inter-laboratory comparability. CONCLUSIONS: Method imprecision was variable. Inter-laboratory performance was reasonably good. However, cases with imprecision and total error above the acceptable limits were apparent for corticosterone and 11-deoxycortisol. Variability did not depend on calibration but apparently on imprecision, accuracy and specificity of individual methods. Tools for improving selectivity and accuracy are required to improve harmonization.


Assuntos
Cortisona , Humanos , Cromatografia Líquida/métodos , Cortodoxona , Corticosterona , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes
15.
Psychopharmacology (Berl) ; 240(1): 157-169, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36520197

RESUMO

RATIONALE: Major depressive disorder (MDD) is one of the most diagnosed mental disorders. Despite this, its pathophysiology remains poorly understood. In this context, basic research aims to unravel the pathophysiological mechanisms of MDD as well as investigate new targets and substances with therapeutic potential. Transient receptor potential ankyrin 1 (TRPA1) is a transmembrane channel considered a sensor for inflammation and oxidative stress. Importantly, both inflammation and oxidative stress have been suggested as participants in the pathophysiology of MDD. However, the potential participation of TRPA1 in depressive disorder remains poorly investigated. OBJECTIVE: To investigate the involvement of the TRPA1 channel in the behavioral changes induced by chronic corticosterone administration (CCA) in male mice. METHODS: Swiss male mice were exposed to 21 days of CCA protocol and then treated with HC-030031 or A-967079, TRPA1 antagonists. Behavioral tests, analyzes of oxidative parameters and TRPA1 immunocontent were performed in the prefrontal cortex (PFC) and hippocampus (HIP). RESULTS: CCA induced despair-like behavior in mice accompanied by an increase in the levels of hydrogen peroxide (H2O2), a TRPA1 agonist, which was reversed by TRPA1 antagonists and ketamine (positive control). In addition, CCA protocol reduced the immunocontent of this channel in the HIP and showed a tendency to increase the TRPA1 protein expression in the PFC. CONCLUSION: Our work suggests that TRPA1 channel appears crucial to mediate the behavioral impairment induced by CCA in male Swiss mice.


Assuntos
Corticosterona , Transtorno Depressivo Maior , Masculino , Animais , Camundongos , Canal de Cátion TRPA1/metabolismo , Peróxido de Hidrogênio/metabolismo , Inflamação
16.
Eur J Pharmacol ; 939: 175437, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36502961

RESUMO

Pimavanserin is a highly selective 5-HT2A inverse agonist in current medical use. Prior studies suggest that 5-HT2A serotonin receptors may play a role in anxiety and emotional memory. Therefore, pimavanserin was tested in a rat model of PTSD to determine whether it might ameliorate PTSD-like symptoms. The lifetime prevalence of PTSD is estimated to be 125% higher in women than men. Consequently, in an effort to create a robust model of PTSD that was more representative of human PTSD prevalence, 20-week old female rats of the emotionally hyperreactive Lewis strain were used for these studies. The rats were single-housed and exposed twice to restraint stress coupled with predator odor or to a sham-stressed condition. Twenty days after the second stress or sham-stress exposure, rats were injected with saline alone or with 0.3 or 1.0 mg/kg pimavanserin, doses that were confirmed to substantially block 5-HT2A receptor activity in this study without causing any non-specific behavioral or adverse effects. One hour later, rats were tested for anxiety through acoustic startle response, the elevated plus-maze and three parameters of open field behavior. Five days later, blood was sampled for plasma corticosterone. The stressed/saline-injected rats had higher anxiety scores and corticosterone levels than sham-stressed/saline-injected rats. Pimavanserin significantly and generally dose-dependently reversed these persistent stress effects, but had no significant effect on the behavioral measures in normal, non-stressed rats. These results, consistent with a role for the 5-HT2A receptor, suggest that pimavanserin might have potential to reduce some consequences of traumatic stress.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Animais , Feminino , Humanos , Masculino , Ratos , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Corticosterona/farmacologia , Modelos Animais de Doenças , Agonismo Inverso de Drogas , Ratos Endogâmicos Lew , Receptor 5-HT2A de Serotonina , Reflexo de Sobressalto , Serotonina/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/etiologia , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico
17.
J Oral Rehabil ; 50(3): 223-233, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36482049

RESUMO

BACKGROUND AND OBJECTIVES: Chronic stress (CS) is closely related to intestinal health. Occlusal disharmony (OD) is a risk factor for hypersensitivity to novel stress, and the relationship between OD and the intestinal system with or without other chronic stresses remains unclear. Therefore, the purpose of this study was to investigate whether OD affects the gut microbiota and the intestinal barrier in a CS-exposed animal model. METHODS: OD was induced by making a 0.5-mm-thick incision on the right maxillary molar. CS involved exposure to one stressor per day for 35 days. Sprague-Dawley rats were randomly divided into an untreated control group and OD-, CS- and OD + CS-treated groups. The behavioural tests, serum corticosterone level, gut microbiota composition and tight junction protein expression in colon tissue were measured on the 56th day to elucidate the effect of OD on animals under CS. RESULTS: Significant differences in performance on behavioural tests and serum corticosterone concentrations were observed on day 56 in the OD + CS group compared with the control group. Exposure to occlusal disharmony or chronic stress resulted in a change in the composition of the gut microbiota of rats. Differences in the expression of the tight junction proteins zonula occludens-1 and junctional adhesion molecule-A were observed in colon tissue from the OD + CS group compared with the control group. CONCLUSIONS: We concluded that the significant changes in performance on behavioural tests, serum corticosterone concentrations and microbiota dysbiosis and tight junction protein levels induced by OD with CS may indicate that OD is a potential factor promoting gut microbiota dysbiosis.


Assuntos
Microbioma Gastrointestinal , Ratos , Animais , Ratos Sprague-Dawley , Disbiose , Corticosterona/farmacologia , Modelos Animais de Doenças , Proteínas de Junções Íntimas
18.
Pharmacol Rep ; 75(1): 85-98, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36586075

RESUMO

BACKGROUND: Long-term cocaine exposure leads to dysregulation of the reward system and initiates processes that ultimately weaken its rewarding effects. Here, we studied the influence of an escalating-dose cocaine regimen on drug-associated appetitive behavior after a withdrawal period, along with corresponding molecular changes in plasma and the prefrontal cortex (PFC). METHODS: We applied a 5 day escalating-dose cocaine regimen in rats. We assessed anxiety-like behavior at the beginning of the withdrawal period in the elevated plus maze (EPM) test. The reinforcement properties of cocaine were evaluated in the Conditioned Place Preference (CPP) test along with ultrasonic vocalization (USV) in the appetitive range in a drug-associated context. We assessed corticosterone, proopiomelanocortin (POMC), ß-endorphin, CART 55-102 levels in plasma (by ELISA), along with mRNA levels for D2 dopaminergic receptor (D2R), κ-receptor (KOR), orexin 1 receptor (OX1R), CART 55-102, and potential markers of cocaine abuse: miRNA-124 and miRNA-137 levels in the PFC (by PCR). RESULTS: Rats subjected to the escalating-dose cocaine binge regimen spent less time in the cocaine-paired compartment, and presented a lower number of appetitive USV episodes. These changes were accompanied by a decrease in corticosterone and CART levels, an increase in POMC and ß-endorphin levels in plasma, and an increase in the mRNA for D2R and miRNA-124 levels, but a decrease in the mRNA levels for KOR, OX1R, and CART 55-102 in the PFC. CONCLUSIONS: The presented data reflect a part of a bigger picture of a multilevel interplay between neurotransmitter systems and neuromodulators underlying processes associated with cocaine abuse.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , MicroRNAs , Ratos , Animais , Pró-Opiomelanocortina , beta-Endorfina , Corticosterona , Recompensa , RNA Mensageiro
19.
Front Endocrinol (Lausanne) ; 13: 1040040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465619

RESUMO

Prior investigation shows an increase in the activity of both hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin system (RAS) in diabetic patients. Moreover, activation of angiotensin-II type 1 receptor (AT1) has been associated with adrenal steroidogenesis. This study investigates the role of RAS on the overproduction of corticosterone in diabetic mice. Diabetes was induced by intravenous injection of alloxan into fasted Swiss-webster mice. Captopril (angiotensin-converting enzyme inhibitor), Olmesartan (AT1 receptor antagonist), CGP42112A (AT2 receptor agonist) or PD123319 (AT2 receptor antagonist) were administered daily for 14 consecutive days, starting 7 days post-alloxan. Plasma corticosterone was evaluated by ELISA, while adrenal gland expressions of AT1 receptor, AT2 receptor, adrenocorticotropic hormone receptor MC2R, pro-steroidogenic enzymes steroidogenic acute regulatory protein (StAR), and 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) were assessed using immunohistochemistry or western blot. Diabetic mice showed adrenal gland overexpression of AT1 receptor, MC2R, StAR, and 11ßHSD1 without altering AT2 receptor levels, all of which were sensitive to Captopril or Olmesartan treatment. In addition, PD123319 blocked the ability of Olmesartan to reduce plasma corticosterone levels in diabetic mice. Furthermore, CGP42112A significantly decreased circulating corticosterone levels in diabetic mice, without altering the overexpression of MC2R and StAR in the adrenal glands. Our findings revealed that inhibition of both angiotensin synthesis and AT1 receptor activity reduced the high production of corticosterone in diabetic mice via the reduction of MC2R signaling expression in the adrenal gland. Furthermore, the protective effect of Olmesartan on the overproduction of corticosterone by adrenals in diabetic mice depends on both AT1 receptor blockade and AT2 receptor activation.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Camundongos , Animais , Sistema Renina-Angiotensina , Glucocorticoides , Corticosterona , Captopril/farmacologia , Aloxano
20.
J Biosci ; 472022.
Artigo em Inglês | MEDLINE | ID: mdl-36550691

RESUMO

Predators are the key regulators of prey populations in different environments. However, they are not always present but often come and go. Moreover, the level of predation risk varies based on habitat complexity, resource availability and other ecological factors. Hence, it is adaptive for prey animals to match their antipredator responses with the level of predation risk as such responses are costly to produce and maintain, and there exists a trade-off between fitness-enhancing and fitness-reducing activities. To test whether larval Indosylvirana adjust their antipredator responses based on the level of predation risk, we designed an experiment in which tadpoles of Indosylvirana indica were exposed to nil, low, moderate or high levels of predation risk to assess the effect of risk on growth, behaviour, morphology and life-history traits. We also determined the whole-body corticosterone levels to assess the physiological changes associated with the level of predation risk. Our results show that the growth rate of tadpoles experiencing varying levels of predation risk was similar although there was a trend towards a higher growth rate at moderate and high risks. Surprisingly, tadpoles experiencing predation risk did not reduce their activity. However, the activity of tadpoles experiencing differential predation risk was comparable. Similarly, the use of shelter was comparable among tadpole groups, with an overall higher level of activity in the afternoon compared to other times. Although a few morphological traits were different among tadpole groups, there was no trend or pattern. Moreover, these morphological alterations did not contribute to overall tadpole shape changes. Physiologically, tadpoles experiencing predation risk had significantly lower levels of corticosterone compared to those without risk. Interestingly, corticosterone titres among tadpoles facing varying levels of predation risk were similar. Metamorphic traits of individuals in the various predation risk groups were significantly different. Tadpoles experiencing moderate and high risks emerged at a larger size, and those experiencing the highest level of risk metamorphosed at the earliest. The results of our study thus show that the antipredator responses of larval I. indica do not match the level of predation risk, indicating that physiological and ecological constraints could limit the extent to which prey species respond to predation risk and its intensity.


Assuntos
Corticosterona , Comportamento Predatório , Animais , Larva , Corticosterona/farmacologia , Ranidae/fisiologia , Ecossistema
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