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1.
Ecotoxicol Environ Saf ; 215: 112108, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33799132

RESUMO

Fluoride which is widespread in our environment and food due to its geological origin and industrial pollution has been identified as a developmental neurotoxicant. Gut-brain axis provides new insight into brain-derived injury. We previously found the psychoactive effects of a probiotic strain, Lactobacillus johnsonii BS15 against fluoride-induced memory dysfunction in mice by modulating the gut-brain axis. In this study, we aimed to detect the link between the reconstruction of gut microbiota and gut-brain axis through which probiotic alleviate fluoride-induced memory impairment. We also added an hour of water avoidance stress (WAS) before behavioral tests and sampling, aiming to demonstrate the preventive effects of the probiotic on fluoride-induced memory impairment after psychological stress. Mice were given fluoridated drinking water (sodium fluoride 100 ppm, corresponding to 37.8 ± 2.4 ppm F¯) for 70 days and administered with PBS or a probiotic strain, Lactobacillus johnsonii BS15 for 28 days prior to and throughout a 70 day exposure to sodium fluoride. Results showed that fluoride increases the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis and reduces the exploration ratio in novel object recognition (NOR) test and the spontaneous exploration during the T-maze test in mice following WAS, which were significantly improved by the probiotic. 16S rRNA sequencing showed a significant separation in ileal microbiota between the fluoride-treated mice and control mice. Lactobacillus was the main targeting bacteria and significantly reduced in fluoride-treated mice. BS15 reconstructed the fluoride-post microbiota and increased the relative abundance of Lactobacillus. D-lactate content and diamine oxidase (DAO) activity, two biomarkers of gut permeability were reduced in the serum of probiotic-inoculated mice. ZO-1, an intestinal tight junction protein was reduced by fluoride in mRNA, and its protein levels were increased by the probiotic treatment. Moreover, the hippocampus which is essential to learning and memory, down-regulated mRNA level of both the myelin-associated glycoprotein (MAG), and protein levels of brain-derived neurotrophic factor (BDNF), including the improvement of cAMP response element-binding protein (CREB) by BS15 in fluoride-exposed mice after WAS. Via spearman correlation analysis, Lactobacillus displayed significantly positive associations with the behavioral tests, levels of nerve development related factors, and intestinal tight junction proteins ZO-1, and negative association with TNF-α of the hippocampus, highlighting regulatory effects of gut bacteria on memory potential and gut barrier. These results suggested the psychoactive effects of BS15 on fluoride-induced memory dysfunction after psychological stress. In addition, there may be some correlations between fluoride-induced memory dysfunction and reconstruction of gut microbiota. AVAILABILITY OF DATA AND MATERIALS: 16S rRNA sequencing reads have uploaded to NCBI. The accession code of 16S rRNA sequencing reads in the National Center for Biotechnology Information (NCBI) BioProject database: PRJNA660154.


Assuntos
Fluoretos/metabolismo , Microbioma Gastrointestinal/fisiologia , Probióticos/farmacologia , Animais , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Lactobacillus/metabolismo , Masculino , Memória , Transtornos da Memória/induzido quimicamente , Camundongos , Microbiota , Sistema Hipófise-Suprarrenal/metabolismo , RNA Ribossômico 16S/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
2.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808529

RESUMO

The most known effects of endogenous Cushing's syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus-pituitary-thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the "central hypothyroidism". These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus-pituitary-thyroid axis activity. During active Cushing's syndrome, the "immunological tolerance" guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing's syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing's syndrome patients, both during the active disease and after its remission.


Assuntos
Síndrome de Cushing/complicações , Síndrome de Cushing/metabolismo , Doenças da Glândula Tireoide/etiologia , Glândula Tireoide/metabolismo , Animais , Síndrome de Cushing/etiologia , Síndrome de Cushing/terapia , Gerenciamento Clínico , Suscetibilidade a Doenças , Glucocorticoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Transdução de Sinais , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/metabolismo , Doenças da Glândula Tireoide/terapia , Testes de Função Tireóidea
3.
Environ Health Prev Med ; 26(1): 31, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33678156

RESUMO

BACKGROUND: The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. METHODS: Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 µg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. RESULTS: Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 µg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. CONCLUSION: These results suggest that exposure to 5 and 50 µg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.


Assuntos
Disruptores Endócrinos/toxicidade , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Infertilidade Masculina/induzido quimicamente , Fenóis/toxicidade , Sulfonas/toxicidade , Testículo/efeitos dos fármacos , Animais , Biomarcadores , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Testículo/metabolismo , Testículo/fisiopatologia , Testes de Toxicidade Crônica
4.
Mayo Clin Proc ; 96(3): 788-814, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33673927

RESUMO

Increased life expectancy combined with the aging baby boomer generation has resulted in an unprecedented global expansion of the elderly population. The growing population of older adults and increased rate of age-related chronic illness has caused a substantial socioeconomic burden. The gradual and progressive age-related decline in hormone production and action has a detrimental impact on human health by increasing risk for chronic disease and reducing life span. This article reviews the age-related decline in hormone production, as well as age-related biochemical and body composition changes that reduce the bioavailability and actions of some hormones. The impact of hormonal changes on various chronic conditions including frailty, diabetes, cardiovascular disease, and dementia are also discussed. Hormone replacement therapy has been attempted in many clinical trials to reverse and/or prevent the hormonal decline in aging to combat the progression of age-related diseases. Unfortunately, hormone replacement therapy is not a panacea, as it often results in various adverse events that outweigh its potential health benefits. Therefore, except in some specific individual cases, hormone replacement is not recommended. Rather, positive lifestyle modifications such as regular aerobic and resistance exercise programs and/or healthy calorically restricted diet can favorably affect endocrine and metabolic functions and act as countermeasures to various age-related diseases. We provide a critical review of the available data and offer recommendations that hopefully will form the groundwork for physicians/scientists to develop and optimize new endocrine-targeted therapies and lifestyle modifications that can better address age-related decline in heath.


Assuntos
Envelhecimento Cognitivo/fisiologia , Disfunção Cognitiva/prevenção & controle , Envelhecimento Saudável/fisiologia , Terapia de Reposição Hormonal/estatística & dados numéricos , Estilo de Vida , Idoso , Terapia Comportamental/estatística & dados numéricos , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo
5.
Eur J Endocrinol ; 184(5): K11-K14, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33667194

RESUMO

Objective: The role of miRNA as endocrine regulators is emerging, and microRNA mir-30b has been reported to repress Mkrn3. However, the expression of miR-30b during male puberty has not been studied. Design and methods: Circulating relative miR-30b expression was assessed in sera of 26 boys with constitutional delay of growth and puberty (CDGP), treated with low-dose testosterone (T) (n =11) or aromatase inhibitor letrozole (Lz) (n =15) for 6 months and followed up to 12 months (NCT01797718). The associations between the relative expression of miR-30b and hormonal markers of puberty were evaluated. Results: During the 12 months of the study, circulating miR-30b expression increased 2.4 ± 2.5 (s.d.) fold (P = 0.008) in all boys, but this change did not correlate with corresponding changes in LH, testosterone, inhibin B, FSH, or testicular volume (P = 0.25-0.96). Lz-induced activation of the hypothalamic-pituitary-gonadal (HPG) axis was associated with more variable miR-30b responses at 3 months (P < 0.05), whereas those treated with T exhibited significant changes in relative miR-30b levels in the course the study (P < 0.01-0.05). Conclusions: Circulating miR-30b expression in boys with CDGP increases in the course of puberty, and appears to be related to the activity of the HPG axis.


Assuntos
MicroRNAs/sangue , Puberdade/sangue , Adolescente , Quimioterapia Combinada , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Gônadas/fisiologia , Transtornos do Crescimento/sangue , Transtornos do Crescimento/complicações , Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Injeções Intramusculares , Letrozol/administração & dosagem , Letrozol/farmacologia , Estudos Longitudinais , Masculino , Puberdade/efeitos dos fármacos , Puberdade/genética , Puberdade Tardia/sangue , Puberdade Tardia/complicações , Puberdade Tardia/tratamento farmacológico , Testosterona/administração & dosagem , Testosterona/farmacologia , Ubiquitina-Proteína Ligases/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-33466883

RESUMO

The synthesis and secretion of cortisol are controlled by the hypothalamic-pituitary-adrenal axis. Cortisol exhibits a proper 24-h circadian rhythm that affects the brain, the autonomic nervous system, the heart, and the vasculature that prepares the cardiovascular system for optimal function during these anticipated behavioral cycles. A literature search was conducted using databases such as Google Scholar, PubMed, and Scopus. Relevant search terms included "circadian rhythm and cardiovascular", "cortisol", "cortisol and acute coronary syndrome", "cortisol and arrhythmias", "cortisol and sudden cardiac death", "cortisol and stroke", and "cardioprotective agents". A total of 120 articles were obtained on the basis of the above search. Lower levels of cortisol were seen at the beginning of sleep, while there was a rise towards the end of sleep, with the highest level reached at the moment the individual wakes up. In the present review, we discuss the role of 11ß-hydroxysteroid dehydrogenase (11ß-HSD1), which is a novel molecular target of interest for treating metabolic syndrome and type-2 diabetes mellitus. 11ß-HSD1 is the major determinant of cortisol excess, and its inhibition alleviates metabolic abnormalities. The present review highlights the role of cortisol, which controls the circadian rhythm, and describes its effect on the cardiovascular system. The review provides a platform for future potential cardioprotective therapeutic agents.


Assuntos
Sistema Cardiovascular , Hidrocortisona , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Ritmo Circadiano , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo
7.
Ecotoxicol Environ Saf ; 208: 111720, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396051

RESUMO

Fine particulate matter (PM2.5), a ubiquitous environmental pollutant, has been indicated to affect thyroid hormone (TH) homeostasis in women, but the detailed mechanism behind this effect remains unclear. The objective of this study was to evaluate the roles of the hypothalamic-pituitary-thyroid (HPT) axis and hepatic transthyretin in the thyroid-disrupting effects of PM2.5. Sprague Dawley rats were treated with PM2.5 (0, 15 and 30 mg/kg) by passive pulmonary inhalation for 49 days; and recovery experimental group rats were dosed with PM2.5 (30 mg/kg) for 35 days, and no treatment was done during the subsequent 14 days. PM2.5 was handled twice a day by passive pulmonary inhalation throughout the study. After treatment, pathological changes were analyzed by performing haemotoxylin and eosin staining, measuring levels of THs and urine iodine (UI) in serum, plasma, and urine samples using enzyme-linked immunoabsorbent assay, and expression of proteins in the hypothalamus, pituitary, thyroid, and liver tissues of rats were analyzed by immunohistochemistry and Western blotting. The levels of oxidative stress factors, such as reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and nuclear factor-kappa B (NF-κB) in female rats' plasma were also evaluated by ELISA. The results of these analyses revealed that PM2.5 treatment induced pathologic changes in rat thyroid and liver characterized by increased follicular cavity size and decreased amounts of follicular epithelial cells and fat vacuoles, respectively. Serum levels of triiodothyronine, thyroxine, and thyroid stimulating hormone were significantly decreased, plasma NF-κB level was increased and plasma redox state was unbalanced (enhanced ROS, MDA and Gpx levels; reduced SOD activities) in female rats treated with PM2.5 (P < 0.05). PM2.5 treatment suppressed the biosynthesis and biotransformation of THs by increasing sodium iodide symporter, thyroid transcription factor 1, thyroid transcription factor 2, and paired box 8 protein expression levels (P < 0.05). Additionally, thyroid stimulating hormone receptor and thyroid peroxidase levels were significantly decreased (P < 0.05). Both thyrotropin releasing hormone receptor and thyroid stimulating hormone beta levels were enhanced (P < 0.05). Moreover, transport of THs was inhibited due to reduced protein expression of hepatic transthyretin upon treatment with PM2.5. In summary, PM2.5 treatment could perturb TH homeostasis by affecting TH biosynthesis, biotransformation, and transport, affecting TH receptor levels, and inducing oxidative stress and inflammatory responses. Activation of the HPT axis and altered hepatic transthyretin levels therefore appear to play a crucial role in PM2.5-induced thyroid dysfunction.


Assuntos
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Material Particulado/toxicidade , Pré-Albumina/metabolismo , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Animais , Feminino , Homeostase/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Material Particulado/química , Ratos , Ratos Sprague-Dawley , Receptores dos Hormônios Tireóideos/metabolismo , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia
8.
Neurosci Lett ; 746: 135618, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33429002

RESUMO

Stress is a common seizure trigger in persons with epilepsy. The body's physiological response to stress is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and involves a hormonal cascade that includes corticotropin releasing hormone (CRH), adrenocorticotropin releasing hormone (ACTH) and the release of cortisol (in humans and primates) or corticosterone (in rodents). The prolonged exposure to stress hormones may not only exacerbate pre-existing medical conditions including epilepsy, but may also increase the predisposition to psychiatric comorbidities. Hyperactivity of the HPA axis negatively impacts the structure and function of the temporal lobe of the brain, a region that is heavily involved in epilepsy and mood disorders like anxiety and depression. Seizures themselves damage temporal lobe structures, further disinhibiting the HPA axis, setting off a vicious cycle of neuronal damage and increasing susceptibility for subsequent seizures and psychiatric comorbidity. Treatments targeting the HPA axis may be beneficial both for epilepsy and for associated stress-related comorbidities such as anxiety or depression. This paper will highlight the evidence demonstrating dysfunction in the HPA axis associated with epilepsy which may contribute to the comorbidity of psychiatric disorders and epilepsy, and propose treatment strategies that may dually improve seizure control as well as alleviate stress related psychiatric comorbidities.


Assuntos
Epilepsia/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Transtornos Mentais/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Hormônio Adrenocorticotrópico/antagonistas & inibidores , Hormônio Adrenocorticotrópico/metabolismo , Animais , Anticonvulsivantes/administração & dosagem , Corticosterona/antagonistas & inibidores , Corticosterona/metabolismo , Desoxicorticosterona/antagonistas & inibidores , Desoxicorticosterona/metabolismo , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Resultado do Tratamento
9.
Res Vet Sci ; 134: 86-95, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360121

RESUMO

Transport stress (TS) in animals lead to change in blood composition, brain structure, and the endocrine system as well as behavior. γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system (CNS), influences many physiological functions and plays a significant role in coping with stress. This study aimed to explore the effect of stress on behavior, HPA axis, GABA transmitters and the distribution of GABAergic interneurons in the prefrontal cortex (PFC) and striatum of the brain by a rat model of simulated transport stress (STS). Thirty-six male Sprague Dawley rats were randomly divided into a control group (n = 12, no stress), a TS1d group (n = 12, 2 h stress for 1 d) and a TS7d group (n = 12, 2 h stress each day for 7 d). After STS, the rats were subjected to open-field testing (OFT) followed by serologic analysis, colorimetry, Western blot and immunohistochemistry. The total score of the OFT showed the similar profile with serum concentrations of corticosterone (CORT) and norepinephrine (NE), which in the TS7d group were all higher than the TS1d group but lower than the control group. STS also reduced GABA, glutamate decarboxylase 67 (GAD67) and GABA transporter 1 (GAT1) expression in the TS1d and these markers were increased in the TS7d, suggesting that GABA was related to hypothalamic-pituitary-adrenal (HPA) axis activation under stress. The number of parvalbumin (PV)-, somatostatin (SOM)-, and calretinin (CR)- positive cells were decreased with stress increase. Our findings revealed that STS affected the behavior of rats, synthesis and release of GABA by altering the HPA axis.


Assuntos
Calbindina 2/metabolismo , Neurônios GABAérgicos/metabolismo , Parvalbuminas/metabolismo , Transdução de Sinais , Estresse Fisiológico , Transportes , Animais , Encéfalo/metabolismo , Corticosterona/sangue , Modelos Animais de Doenças , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Somatostatina/metabolismo , Ácido gama-Aminobutírico/metabolismo
11.
Physiol Rep ; 8(24): e14644, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33340273

RESUMO

This review examines the stress hormone cortisol which plays an important role in regulating and supporting different bodily functions. Disruption in cortisol production has an impact on health and this review looks at a wide range of papers where cortisol has been indicated as a factor in numerous chronic conditions-especially those which are classed as "noncommunicable diseases" (NCDs). Timely detection, screening, and treatment for NCDs are vital to address the growing problem of NCDs worldwide-this would have health and socioeconomic benefits. Interestingly, many of the papers highlight the pro-inflammatory consequences of cortisol dysregulation and its deleterious effects on the body. This is particularly relevant given the recent findings concerning COVID-19 where pro-inflammatory cytokines have been implicated in severe inflammation.


Assuntos
/sangue , Doenças Cardiovasculares/sangue , Ritmo Circadiano , Diabetes Mellitus Tipo 2/sangue , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Inflamação/sangue , Estresse Fisiológico , Animais , Biomarcadores/sangue , /fisiopatologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Citocinas/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Inflamação/epidemiologia , Inflamação/fisiopatologia , Mediadores da Inflamação/sangue
12.
Zhongguo Zhong Yao Za Zhi ; 45(20): 4971-4977, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33350271

RESUMO

This study aimed to investigate the antidepressant effects of Puyu Capsules and its potential mechanism. The antidepressant activity of Puyu Capsules was evaluated by forced swimming test(FST) and tail suspension test(TST) after subchronic administration in mice. Next, the mice were subjected to a chronic unpredictable stress(CUS) protocol for a period of 28 d to induce depressive-like behaviors. Then, a sucrose preference test, open-field test and novelty-suppressed feeding test were performed to evaluate the antidepressant effect of Puyu Capsules. After the behavioral test, the adrenal index was calculated; the levels of serum corticosterone(CORT) and adrenocorticotropic hormone(ACTH) were detected by enzyme-linked immunosorbent assay(ELISA); the levels of glucocorticoid receptor(GR), protein expression of brain-derived neurotrophic factor(BDNF), and the ratio of phosphorylated cAMP response element binding protein(CREB) to total CREB were detected by Western blot to explore the antidepressant function and mechanism of Puyu Capsules. The results suggested that Puyu Capsules had significant antidepressant effects on both the depression model and CUS model. At the same time, the drug could prevent the change of adrenal index induced by CUS and reverse the abnormal activation of CORT and ACTH in the serum of depressed mice. Finally, Puyu Capsules could also reverse the lower expression of pCREB, BDNF and GR in the hippocampus of CUS mice. In conclusion, Puyu Capsules produced significant antidepressant effects, and the mechanism was closely related to hypothalamic pituitary adrenal(HPA) axis activity, GR and CREB-BDNF pathway expression.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Sistema Hipotálamo-Hipofisário , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cápsulas , Depressão/tratamento farmacológico , Depressão/genética , Modelos Animais de Doenças , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Camundongos , Sistema Hipófise-Suprarrenal/metabolismo , Estresse Psicológico
13.
Eur J Endocrinol ; 183(6): 669-676, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33112256

RESUMO

Context: Obesity and cardiometabolic diseases are associated with higher long-term glucocorticoid levels, measured as scalp hair cortisol (HairF) and cortisone (HairE). Cardiometabolic diseases have also been associated with copeptin, a stable surrogate marker for the arginine-vasopressin (AVP) system. Since AVP is, together with corticotropin-releasing hormone (CRH) an important regulator of the hypothalamic-pituitary adrenal axis (HPA axis), we hypothesize that AVP contributes to chronic hypercortisolism in obesity. Objective: To investigate whether copeptin levels are associated with Higher HairF and HairE levels in obesity. Design: A cross-sectional study in 51 adults with obesity (BMI ≥30 kg/m2). Methods: Associations and interactions between copeptin, HairF, HairE, and cardiometabolic parameters were cross-sectionally analyzed. Results: Copeptin was strongly associated with BMI and waist circumference (WC) (rho = 0.364 and 0.530, P = 0.008 and <0.001, respectively), also after correction for confounders. There were no associations between copeptin and HairF or HairE on a continuous or dichotomized scale, despite correction for confounders. Conclusion: In patients with obesity, AVP seems not a major contributor to the frequently observed high cortisol levels. Other factors which stimulate the HPA axis or affect cortisol synthesis or breakdown may be more important than the influence of AVP on long-term glucocorticoid levels in obesity.


Assuntos
Cortisona/metabolismo , Síndrome de Cushing/etiologia , Glicopeptídeos/metabolismo , Hidrocortisona/metabolismo , Obesidade/metabolismo , Adulto , Arginina Vasopressina/metabolismo , Biomarcadores/metabolismo , Índice de Massa Corporal , Hormônio Liberador da Corticotropina/metabolismo , Estudos Transversais , Feminino , Glucocorticoides/metabolismo , Cabelo/química , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Obesidade/complicações , Sistema Hipófise-Suprarrenal/metabolismo
14.
BMC Med Genet ; 21(1): 184, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957930

RESUMO

BACKGROUND: Two important aspects for the development of anxiety disorders are genetic predisposition and alterations in the hypothalamic-pituitary-adrenal (HPA) axis. In order to identify genetic risk-factors for anxiety, the aim of this exploratory study was to investigate possible relationships between genetic polymorphisms in genes important for the regulation and activity of the HPA axis and self-assessed anxiety in healthy individuals. METHODS: DNA from 72 healthy participants, 37 women and 35 men, were included in the analyses. Their DNA was extracted and analysed for the following Single Nucleotide Polymorphisms (SNP)s: rs41423247 in the NR3C1 gene, rs1360780 in the FKBP5 gene, rs53576 in the OXTR gene, 5-HTTLPR in SLC6A4 gene and rs6295 in the HTR1A gene. Self-assessed anxiety was measured by the State and Trait Anxiety Inventory (STAI) questionnaire. RESULTS: Self-assessed measure of both STAI-S and STAI-T were significantly higher in female than in male participants (p = 0.030 and p = 0.036, respectively). For SNP rs41423247 in the NR3C1 gene, there was a significant difference in females in the score for STAI-S, where carriers of the G allele had higher scores compared to the females that were homozygous for the C allele (p < 0.01). For the SNP rs53576 in the OXTR gene, there was a significant difference in males, where carriers of the A allele had higher scores in STAI-T compared to the males that were homozygous for the G allele (p < 0.01). CONCLUSION: This study shows that SNP rs41423247 in the NR3C1 gene and SNP rs53576 in the OXTR gene are associated with self-assessed anxiety in healthy individuals in a gender-specific manner. This suggests that these SNP candidates are possible genetic risk-factors for anxiety.


Assuntos
Transtornos de Ansiedade/genética , Predisposição Genética para Doença/genética , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Polimorfismo de Nucleotídeo Único , Receptores de Glucocorticoides/genética , Receptores de Ocitocina/genética , Adulto , Alelos , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
15.
ACS Chem Neurosci ; 11(13): 1868-1870, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32605374

RESUMO

Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.


Assuntos
Betacoronavirus/metabolismo , Infecções por Coronavirus/metabolismo , Citocinas/metabolismo , Pneumonia Viral/metabolismo , Núcleo Solitário/metabolismo , Axônios/imunologia , Axônios/metabolismo , Axônios/virologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Nervos Cranianos/imunologia , Nervos Cranianos/metabolismo , Nervos Cranianos/virologia , Citocinas/imunologia , Humanos , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/virologia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Pandemias , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/virologia , Pneumonia Viral/imunologia , Núcleo Solitário/imunologia , Núcleo Solitário/virologia
16.
Am J Physiol Heart Circ Physiol ; 319(2): H488-H506, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618516

RESUMO

Although chronic stress is an important risk factor for cardiovascular diseases (CVD) onset, the underlying mechanisms driving such pathophysiological complications remain relatively unknown. Here, dysregulation of innate stress response systems and the effects of downstream mediators are strongly implicated, with the vascular endothelium emerging as a primary target of excessive glucocorticoid and catecholamine action. Therefore, this review article explores the development of stress-related endothelial dysfunction by focusing on the following: 1) assessing the phenomenon of stress and complexities surrounding this notion, 2) discussing mechanistic links between chronic stress and endothelial dysfunction, and 3) evaluating the utility of various preclinical models currently employed to study mechanisms underlying the onset of stress-mediated complications such as endothelial dysfunction. The data reveal that preclinical models play an important role in our efforts to gain an increased understanding of mechanisms underlying stress-mediated endothelial dysfunction. It is our understanding that this provides a good foundation going forward, and we propose that further efforts should be made to 1) more clearly define the concept of stress and 2) standardize protocols of animal models with specific guidelines to better indicate the mental complications that are simulated.


Assuntos
Doenças Cardiovasculares/etiologia , Endotélio Vascular/fisiopatologia , Estresse Psicológico/complicações , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/psicologia , Catecolaminas/metabolismo , Doença Crônica , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Glucocorticoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Fatores de Risco , Transdução de Sinais , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia
17.
PLoS One ; 15(6): e0233718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497103

RESUMO

BACKGROUND: Person and environment-related childhood adverse events have been demonstrated to increase the risk of impaired mental health in later life differently for boys and girls. Altered hypothalamic pituitary adrenal (HPA)-axis functioning has been suggested as a key mechanism underlying this association. Cortisol and dehydroepiandrosterone (DHEA) are both output hormones of the HPA-axis. DHEA may have a protective function against long-term exposure to increased levels of cortisol, but has been little investigated in relation to childhood adversity. OBJECTIVE: We aimed to test the associations between person-, and environment-related childhood adversity and levels of cortisol, DHEA and cortisol/DHEA ratio in adolescent boys and girls. METHODS: A total of 215 Dutch adolescents participated in the study and filled out the 27-item Adverse Life Events Questionnaire for the assessment of childhood adversity, which was split up in separate scores for person-related and environment-related events. Cortisol and DHEA concentrations and cortisol/DHEA ratio were determined in proximal 3 cm long hair segments. Additionally, saliva samples were collected immediately and 30 minutes after waking up, at noon and at 8 pm. Multiple linear regression analyses were used to test associations between childhood adversity and cortisol and DHEA concentrations, for boys and girls separately, with age, BMI and pubertal development as covariates. RESULTS: Data were available for 74 boys and 116 girls with a mean age of 15.7 years (SD = 2.0). Higher levels of person-related childhood adversity were associated with higher hair DHEA levels in girls and with higher hair cortisol levels in boys. A trend towards a significant association was observed between higher levels of environment-related childhood adversity and higher DHEA levels in boys. Neither person- nor environment related childhood adversity was associated with cortisol/DHEA ratio. A trend was observed for environment-related childhood adversity and lower daily cortisol output in boys. CONCLUSION: We found differential associations between childhood adversity and cortisol and DHEA levels in girls and boys, for respectively person-related and environment-related childhood adversity. Our findings suggest that different types of childhood adversity are not only linked to levels of cortisol, but also to DHEA concentrations, in a sex-specific manner, with possible future implications for mental health.


Assuntos
Experiências Adversas da Infância , Desidroepiandrosterona/análise , Hidrocortisona/análise , Adolescente , Desidroepiandrosterona/metabolismo , Feminino , Cabelo/química , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Saliva/química , Autorrelato , Fatores Sexuais , Estresse Psicológico/metabolismo
18.
BMC Cardiovasc Disord ; 20(1): 245, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32450805

RESUMO

BACKGROUND: Cortisol is the main stress hormone mobilised during surgery to establish homeostasis. Our current understanding of the hypothalamic-pituitary-adrenal axis physiology in children undergoing cardiopulmonary bypass is very limited due to: (1) very few cortisol time point measurements over long periods (2) difficulties of sampling in low weight babies and (3) the concomitant use of glucocorticoids at anaesthesia induction. This lack of understanding is reflected in a lack of consensus on the utility of glucocorticoids perioperatively in cardiac surgery with the use of cardiopulmonary bypass. METHODS: The Peacock Study is a prospective, two-centre, observational cohort study of 78 children (undergoing cardiopulmonary bypass procedures and non-surgical procedures - split by age/cyanosis) that aims to characterise in detail the hypothalamic-pituitary-adrenal axis physiology of children using the stress model of paediatric cardiac surgery. Also, we aim to correlate cortisol profiles with clinical outcome data. We herein describe the main study design and report the full cortisol profile of one child undergoing heart surgery, thus proving the feasibility of the method. RESULTS: We used an automated, 24-h tissue microdialysis system to measure cortisol and cortisone, every 20 min. We herein report one cortisol profile of a child undergoing heart surgery. Besides, we measured serum cortisol and adrenocorticotrophic hormone at seven-time points for correlation. Tissue concentrations of cortisol increased markedly several hours after the end of surgery. We also noted an increase in the tissue cortisol/cortisone ratio during this response. CONCLUSION: We report for the first time, the use of an automated microdialysis sampling system to evaluate the paediatric adrenal response in children. Changes in cortisol and cortisone could be measured, and the concentration of cortisol in the tissues increased after the end of cardiac surgery. The method has wide application to measure other hormones dynamically and frequently without the limitation of the circulating blood volume. The data from the main study will clarify how these cortisol profiles vary with age, pathology, type of procedure and correlation to clinical outcomes. TRIAL REGISTRATION: ISCRTN registry, number: 982586.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cortisona/metabolismo , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Adolescente , Fatores Etários , Biomarcadores/metabolismo , Ponte Cardiopulmonar , Criança , Pré-Escolar , Inglaterra , Estudos de Viabilidade , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Lactente , Recém-Nascido , Masculino , Microdiálise , Sistema Hipófise-Suprarrenal/fisiopatologia , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento
19.
Toxicol Lett ; 331: 33-41, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32445661

RESUMO

This study was intended to demonstrate that prenatal dexamethasone exposure (PDE) can induce low basal activity of the hypothalamic-pituitary-adrenal axis (HPAA) in male offspring rats and explore the underlying mechanism. Pregnant rats were subcutaneously administered 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 to GD20. Male GD20 fetuses and postnatal day 85 adult male offspring rats were sacrificed under anesthesia. Hypothalamic cells were from GD20∼postnatal day (PD) 7 fetal male rats, treated with different concentrations of dexamethasone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. The results suggested that dexamethasone enhanced the expression of hypothalamic L-glutamic acid decarboxylase (GAD) 67 by activating GR, further stimulating the conversion of glutamate to gamma-aminobutyric acid (GABA) and inducing an imbalance in glutamatergic/GABAergic afferents in the hypothalamic paraventricular nucleus (PVN). This imbalance change was maintained postnatally, leading to the inhibition of parvocellular neurons, and mediating the low basal activity of the HPAA in PDE offspring rats, which was manifested by decreased levels of blood adrenocorticotropic hormone and corticosterone as well as reduced expression levels of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus. Programming of a developmental imbalance in glutamatergic/GABAergic afferents in the PVN is a potential mechanism responsible for low basal activity of the HPAA in male PDE rats.


Assuntos
Dexametasona/toxicidade , Ácido Glutâmico/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ácido gama-Aminobutírico/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Animais Recém-Nascidos , Arginina Vasopressina/metabolismo , Corticosterona/sangue , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/metabolismo , Glutamato Descarboxilase/metabolismo , Sistema Hipotálamo-Hipofisário/embriologia , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Neurônios Aferentes/metabolismo , Núcleo Hipotalâmico Paraventricular/embriologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Sistema Hipófise-Suprarrenal/embriologia , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos
20.
Am J Physiol Endocrinol Metab ; 319(1): E81-E90, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32396496

RESUMO

We have previously shown that systemic injection of erythropoietin-producing hepatocellular receptor A7 (EPHA7)-Fc raises serum luteinizing hormone (LH) levels before ovulation in female rats, indicating the induction of EPHA7 in ovulation. In this study, we aimed to identify the mechanism and hypothalamus-pituitary-ovary (HPO) axis level underlying the promotion of LH secretion by EPHA7. Using an ovariectomized (OVX) rat model, in conjunction with low-dose 17ß-estradiol (E2) treatment, we investigated the association between EPHA7-ephrin (EFN)A5 signaling and E2 negative feedback. Various rat models (OVX, E2-treated OVX, and abarelix treated) were injected with the recombinant EPHA7-Fc protein through the caudal vein to investigate the molecular mechanism underlying the promotion of LH secretion by EPHA7. Efna5 was observed strongly expressed in the arcuate nucleus of the female rat by using RNAscope in situ hybridization. Our results indicated that E2, combined with estrogen receptor (ER)α, but not ERß, inhibited Efna5 and gonadotropin-releasing hormone 1 (Gnrh1) expressions in the hypothalamus. In addition, the systemic administration of EPHA7-Fc restrained the inhibition of Efna5 and Gnrh1 by E2, resulting in increased Efna5 and Gnrh1 expressions in the hypothalamus as well as increased serum LH levels. Collectively, our findings demonstrated the involvement of EPHA7-EFNA5 signaling in the regulation of LH and the E2 negative feedback pathway in the hypothalamus, highlighting the functional role of EPHA7 in female reproduction.


Assuntos
Efrina-A5/metabolismo , Receptor alfa de Estrogênio/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Hormônio Luteinizante/metabolismo , Precursores de Proteínas/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/metabolismo , Efrina-A5/efeitos dos fármacos , Efrina-A5/genética , Estradiol/farmacologia , Receptor beta de Estrogênio/metabolismo , Estrogênios/farmacologia , Retroalimentação Fisiológica/efeitos dos fármacos , Retroalimentação Fisiológica/fisiologia , Feminino , Hormônio Liberador de Gonadotropina/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/efeitos dos fármacos , Hormônio Luteinizante/efeitos dos fármacos , Oligopeptídeos/farmacologia , Ovariectomia , Ovário/efeitos dos fármacos , Ovário/metabolismo , Precursores de Proteínas/efeitos dos fármacos , Ratos , Receptor EphA7/genética , Receptor EphA7/metabolismo , Receptor EphA7/farmacologia , Proteínas Recombinantes
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