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1.
Ecotoxicol Environ Saf ; 208: 111464, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33075589

RESUMO

Ambient fine particulate matter (PM2.5) exposure correlates with adverse cardiometabolic effects. The underlying mechanisms have not yet been fully understood. Hypothalamic-pituitary-adrenal (HPA) axis, as the central stress response system, regulates cardiometabolic homeostasis and is implicated in the progression of various adverse health effects caused by inhalational airborne pollutant exposure. In this study, we investigated whether ambient PM2.5 exposure activates HPA axis and its effect mediating PM2.5-induced pulmonary inflammation. C57Bl/6 J mice were intratracheally instilled with different concentrations of diesel exhaust PM2.5 (DEP), and plasma was harvested at different times. Assessments of plasma stress hormones revealed that DEP instillation dose- and time-dependently increased mouse circulating corticosterone and adrenocorticotropic hormone (ACTH) levels, strongly supporting that DEP instillation activates HPA axis. To determine which components of DEP activate HPA axis, C57Bl/6J mice were intratracheally instilled with water-soluble and -insoluble fractions of DEP. Plasma analyses showed that water-insoluble but not -soluble fraction of DEP increased circulating corticosterone and ACTH levels. Consistently, concentrated ambient PM2.5 (CAP) exposure significantly increased mouse urine and hair corticosterone levels, corroborating the activation of HPA axis by ambient PM2.5. Furthermore, deletion of stress hormones by total bilateral adrenalectomy alleviated PM2.5-induced pulmonary inflammation, providing insights into the contribution of central neurohormonal mechanisms in modulating adverse health effects caused by exposure to PM2.5.


Assuntos
Poluentes Atmosféricos/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Material Particulado/toxicidade , Pneumonia/induzido quimicamente , Animais , Corticosterona/sangue , Exposição por Inalação/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Emissões de Veículos/análise
2.
Nat Commun ; 11(1): 6295, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293550

RESUMO

The central melanocortin system plays a fundamental role in the control of feeding and body weight. Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) also regulate overall glucose homeostasis via insulin-dependent and -independent pathways. Here, we report that a subset of ARC POMC neurons innervate the liver via preganglionic parasympathetic acetylcholine (ACh) neurons in the dorsal motor nucleus of the vagus (DMV). Optogenetic stimulation of this liver-projecting melanocortinergic pathway elevates blood glucose levels that is associated with increased expression of hepatic gluconeogenic enzymes in female and male mice. Pharmacological blockade and knockdown of the melanocortin-4 receptor gene in the DMV abolish this stimulation-induced effect. Activation of melanocortin-4 receptors inhibits DMV cholinergic neurons and optogenetic inhibition of liver-projecting parasympathetic cholinergic fibers increases blood glucose levels. This elevated blood glucose is not due to altered pancreatic hormone release. Interestingly, insulin-induced hypoglycemia increases ARC POMC neuron activity. Hence, this liver-projecting melanocortinergic circuit that we identified may play a critical role in the counterregulatory response to hypoglycemia.


Assuntos
Glicemia/metabolismo , Hipoglicemia/etiologia , Fígado/inervação , Pró-Opiomelanocortina/metabolismo , Nervo Vago/metabolismo , Acetilcolina/metabolismo , Potenciais de Ação/fisiologia , Animais , Núcleo Arqueado do Hipotálamo/citologia , Núcleo Arqueado do Hipotálamo/metabolismo , Glicemia/análise , Neurônios Colinérgicos/metabolismo , Corticosterona/sangue , Corticosterona/metabolismo , Modelos Animais de Doenças , Vias Eferentes/fisiologia , Feminino , Técnicas de Silenciamento de Genes , Glucagon/sangue , Glucagon/metabolismo , Gluconeogênese/genética , Humanos , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Insulina/sangue , Insulina/metabolismo , Fígado/enzimologia , Masculino , Camundongos , Optogenética , RNA Mensageiro/metabolismo , Receptor Tipo 4 de Melanocortina/antagonistas & inibidores , Receptor Tipo 4 de Melanocortina/genética , Receptor Tipo 4 de Melanocortina/metabolismo , Regulação para Cima , Nervo Vago/citologia
3.
Sci Rep ; 10(1): 16813, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033347

RESUMO

Here we investigate the stress-signaling responsible for the effects of acute/repeated psychological stresses (the most common stresses in human society) on spermatozoa number and functionality, as well as the transcriptional profile of mitochondrial dynamics markers by using the in vivo and ex vivo approaches. Acute and repeated stress inhibit spermatozoa functionality (acute -> 3.2-fold, repeated -> 2.5-fold), while only repeated stress reduces the spermatozoa number (1.7-fold). Stress hormones mimic these effects and decrease the spermatozoa functionality (adrenaline: 10 µM -> 2.4-fold, 100 µM - > 2.8-fold; hydrocortisone: 50 pM -> 2.7-fold, 500 pM -> 8.5-fold). They also significantly disturb the transcriptional profile of all main mitochondrial dynamics markers in spermatozoa. Ex vivo manipulation of stress signaling in spermatozoa reveals that most of these effects are mediated through ɑ1-and/or-ß-adrenergic receptors. The transcription of these receptors and their kinases in the same samples is under the significant influence of adrenergic signaling. Our results are the first to show the importance of mitochondrial dynamics markers in spermatozoa since the transcriptional profiles of sixteen-out-of-ninteen are disturbed by manipulation of stress-hormones-signaling. This is a completely new molecular approach to assess spermatozoa functionality and it is important for a better understanding of the correlations between stress, environmental-life-style and other factors, and male (in)fertility.


Assuntos
Dinâmica Mitocondrial , Receptores Adrenérgicos/metabolismo , Espermatozoides/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Biomarcadores , Corticosterona/sangue , Di-Hidrotestosterona/sangue , Epinefrina/sangue , Perfilação da Expressão Gênica , Imobilização/psicologia , Masculino , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/fisiologia , Ratos , Ratos Wistar , Espermatozoides/metabolismo , Estresse Psicológico/sangue , Estresse Psicológico/metabolismo , Testosterona/sangue
4.
Sci Rep ; 10(1): 16315, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004871

RESUMO

The glucocorticoid stress response is frequently used to indicate vertebrate response to the environment. Body temperature may affect glucocorticoid concentrations, particularly in ectotherms. We conducted lab manipulations and field measurements to test the effects of body temperature on plasma corticosterone (predominant glucocorticoid in reptiles) in eastern fence lizards (Sceloporus undulatus). First, we acclimated lizards to one of 4 treatments: 22 °C, 29 °C, 33 °C, or 36 °C, and measured cloacal temperatures and plasma corticosterone concentrations at baseline and after exposure to a standardized stressor (cloth bag). Both baseline and stress-induced corticosterone concentrations were lower in lizards with lower body temperatures. Second, we acclimated lizards to 22 °C or 29 °C and exposed them to a standardized (cloth bag) stressor for 3 to 41 min. Lizards acclimated to 29 °C showed a robust increase in plasma corticosterone concentrations with restraint stress, but those at 22 °C showed no such increases in corticosterone concentrations. Third, we measured lizards upon capture from the field. There was no correlation between body temperature and baseline plasma corticosterone in field-caught lizards. These results suggest body temperature can significantly affect plasma corticosterone concentrations in reptiles, which may be of particular concern for experiments conducted under laboratory conditions but may not translate to the field.


Assuntos
Corticosterona/sangue , Lagartos/sangue , Animais , Temperatura Corporal , Feminino , Lagartos/fisiologia , Masculino , Estresse Fisiológico , Temperatura
5.
Life Sci ; 262: 118516, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011220

RESUMO

Swim therapy in the form of moderate physical activity has general health benefits. Regular exercise prevents the progression of chronic diseases affecting the different bodily systems. The metabolic alterations associated with following such lifestyle remain not fully understood. The aim of the present study was to elucidate the metabolic changes following prolonged swim therapy. Twenty-four Sprague Dawley rats were divided into sedentary and exercise groups. Our results revealed that regular exercise significantly increased the serum levels of growth hormone (GH), glucagon and corticosterone. A reduction in the circulating levels of irisin and insulin hormones, and glucose were noticed alongside with an upregulation in the mRNA expression levels of FNDC5, PGC-1α, GLUT-4 and preptin receptors with downregulation in the expression of Enho gene in the heart of exercised rats. Liver of the exercised rats showed elevation in the transcriptional levels of Enho gene, PPARα, and preptin with reduction in the transcriptional levels of preptin receptors. Exercise induced an increase in the pancreatic mRNA of Enho gene, preptin and preptin receptors, and a reduction in FNDC5, PPARα and PGC-1α. An elevation in the gastrocnemius muscle PGC-1α mRNA expression and a decline in the soleus muscle Enho mRNA were found. Exercise diminishes the activities of SOD, CAT and GPx in the gastrocnemius muscle, liver and pancreas. Myogenin expression increased in all examined skeletal muscles. This study takes into account the complex crosstalk between different signaling pathways in skeletal muscles, heart, liver and pancreas as well as the metabolic alterations in response to regular exercise.


Assuntos
Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Natação/fisiologia , Animais , Corticosterona/sangue , Regulação da Expressão Gênica/fisiologia , Glucagon/sangue , Hormônio do Crescimento/sangue , Masculino , Ratos , Ratos Sprague-Dawley
6.
PLoS One ; 15(10): e0240176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022690

RESUMO

The use of carbon dioxide (CO2) exposure as a means of animal euthanasia has received considerable attention in mammals and birds but remains virtually untested in reptiles. We measured the behavioral responses of four squamate reptile species (Homalopsis buccata, Malayopython reticulatus, Python bivitattus, and Varanus salvator) to exposure to 99.5% CO2 for durations of 15, 30, or 90 minutes. We also examined alterations in plasma corticosterone levels of M. reticulatus and V. salvator before and after 15 minutes of CO2 exposure relative to control individuals. The four reptile taxa showed consistent behavioral responses to CO2 exposure characterized by gaping and minor movements. The time taken to lose responsiveness to stimuli and cessation of movements varied between 240-4260 seconds (4-71 minutes), with considerable intra- and inter-specific variation. Duration of CO2 exposure influenced the likelihood of recovery, which also varied among species (e.g., from 0-100% recovery after 30-min exposure). Plasma corticosterone concentrations increased after CO2 exposure in both V. salvator (18%) and M. reticulatus (14%), but only significantly in the former species. Based on our results, CO2 appears to be a mild stressor for reptiles, but the relatively minor responses to CO2 suggest it may not cause considerable distress or pain. However, our results are preliminary, and further testing is required to understand optimal CO2 delivery mechanisms and interspecific responses to CO2 exposure before endorsing this method for reptile euthanasia.


Assuntos
Dióxido de Carbono/toxicidade , Corticosterona/sangue , Movimento , Répteis/fisiologia , Animais
7.
Am Nat ; 196(4): 487-500, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32970461

RESUMO

AbstractEvolution of adaptation requires predictability and recurrence of functional contexts. Yet organisms live in multifaceted environments that are dynamic and ever changing, making it difficult to understand how complex adaptations evolve. This problem is particularly apparent in the evolution of adaptive maternal effects, which are often assumed to require reliable and discrete cues that predict conditions in the offspring environment. One resolution to this problem is if adaptive maternal effects evolve through preexisting, generalized maternal pathways that respond to many cues and also influence offspring development. Here, we assess whether an adaptive maternal effect in western bluebirds is influenced by maternal stress pathways across multiple challenging environments. Combining 18 years of hormone sampling across diverse environmental contexts with an experimental manipulation of the competitive environment, we show that multiple environmental factors influenced maternal corticosterone levels, which, in turn, influenced a maternal effect on aggression of sons in adulthood. Together, these results support the idea that multiple stressors can induce a known maternal effect in this system. More generally, they suggest that activation of general pathways, such as the hypothalamic-pituitary-adrenal axis, may simplify and facilitate the evolution of adaptive maternal effects by integrating variable environmental conditions into preexisting maternal physiological systems.


Assuntos
Herança Materna , Aves Canoras/fisiologia , Estresse Fisiológico , Adaptação Fisiológica , Agressão , Animais , Corticosterona/sangue , Feminino , Masculino , Montana , Fenótipo
8.
Life Sci ; 260: 118432, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32941895

RESUMO

AIMS: Biological, psychosocial and lifestyle risk factors interact in the development of type 2 diabetes mellitus (T2DM). To date, the effects of sex, chronic stress (CS) and high-fat diet (HFD) on T2DM and the ability of linalyl acetate (LA) to prevent T2DM have not been determined. This study therefore explored the differential effects of CS and HFD on T2DM, as well as the ability of LA to prevent T2DM development, in male and female rats. MAIN METHODS: T2DM was induced in rats by feeding an HFD and placing them under immobilization stress for 2 h/day for 3 weeks. Low-dose streptozotocin was administered on day 15, and LA was administered for 3 weeks. KEY FINDINGS: Fasting blood sugar (FBS) increased in HFD-fed male, but not female, rats. CS further increased FBS in HFD-fed rats, whereas CS alone did not alter FBS. The homeostatic model assessment-insulin resistance (HOMA-IR) showed results similar to FBS. Serum corticosterone levels markedly increased only in HFD-fed male rats exposed to CS. Pancreas nuclear factor kappa B (NF-κB) levels were higher in HFD-fed male rats exposed to CS than in control rats although there were no sex differences. LA 10 mg/kg significantly reduced FBS, serum insulin, HOMA-IR, and serum corticosterone levels in HFD-fed male rats exposed to CS. LA 10 mg/kg also tended to reduce NF-κB in the pancreas and significantly increased mitochondrial membrane potential (MMP) in the liver. SIGNIFICANCE: Male rats are vulnerable to T2DM induced by CS and HFD, and LA can prevent T2DM in these rats not only by reducing insulin resistance and corticosterone levels but by increasing MMP in the liver.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Monoterpenos/farmacologia , Animais , Corticosterona/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Insulina/sangue , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Fatores Sexuais , Estreptozocina/administração & dosagem , Estreptozocina/toxicidade , Estresse Fisiológico
9.
Sci Rep ; 10(1): 15884, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985516

RESUMO

It is a common fact, that the content of sex hormones in humans and animals varies in different age periods. The functional state of the immune system also changes with age. However, sex differences studies of inflammatory and immune responses during puberty prevail in literature. Investigation of immune responses to LPS peculiarities in prepubertal females and males may contribute to the development of more effective immunotherapy and minimize side effects of children vaccination. Therefore, the aim of this work was to investigate the LPS-induced SIRS sex differences in prepubertal Wistar rats. Despite the absence of sex differences in estradiol and testosterone levels, LPS-induced inflammatory changes in liver and lungs are more pronounced among males. Males demonstrate the increasing neopterin, corticosterone levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Not less important is that in females, demonstrating less morphological changes in liver and lungs, endotoxin level is tenfold higher, and corticosterone level decreases. Thus, endotoxin cannot be used as a marker of the severity of multiple organ failure in prepubertal period. The LPS-induced immune reactions in females and males are similar and are characterized by immunosuppression. Both females and males have decreased production of cytokines (IL-2, IL-4, TNF-α, TGF-ß) and the absolute number of CD3 + and CD3 + CD8 + lymphocytes in blood. The acute atrophy of thymus and apoptosis of thymic cells are revealed in animals of both sexes. However, the number of CD3 + CD4 + T-helpers and CD4 + CD25 + Foxp3 + T-cells decreases only in females with SIRS, and in males there was a decrease of CD45R + B-cells. The least expressed sex differences in immune responses in the prepubertal period can be determined by the low levels of sex steroids and the absence of their immunomodulatory effect. Further studies require the identification of mechanisms, determining the sex differences in the inflammatory and immune responses in prepubertal animals.


Assuntos
Imunidade/fisiologia , Fígado/imunologia , Pulmão/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Animais , Corticosterona/sangue , Endotoxinas/sangue , Estradiol/sangue , Feminino , Fígado/patologia , Pulmão/patologia , Masculino , Ratos , Ratos Wistar , Fatores Sexuais , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/patologia , Testosterona/sangue
10.
Biochim Biophys Acta Mol Basis Dis ; 1866(11): 165914, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768678

RESUMO

Chagas disease, triggered by the flagellate protozoan Trypanosoma cruzi (T. cruzi) plays a potentially threat to historically non-endemic areas. Considerable evidence established that the immuno-endocrine balance could deeply influence the experimental T. cruzi progression inside the host's body. A high-resolution multiple reaction monitoring approach (MRMHR) was used to study the influence of melatonin on adrenal and plasma steroidal hormones profile of T. cruzi infected Wistar rats. Young (5 weeks) and middle-aged (18 months) male Wistar rats received melatonin (5 mg/Kg, orally) during the acute Chagas disease. Corticosterone, 11-dehydrocorticosterone (11-DHC), cortisol, cortisone, aldosterone, progesterone and melatonin concentration were evaluated. Interleukin-1 alpha and ß (IL-1α and ß), IL-6 and transforming growth factor beta (TGF-ß) were also analyzed. Our results revealed an increased production of corticosterone, cortisone, cortisol and aldosterone in middle-aged control animals, thus confirming the aging effects on the steroidal hormone profile. Serum melatonin levels were reduced with age and predominantly higher in young and middle-aged infected rats. Melatonin treatment reduced the corticosterone, 11-DHC, cortisol, cortisone, aldosterone and progesterone in response to T. cruzi infection. Decreased IL-1 α and ß concentrations were also found in melatonin treated middle-aged infected animals. Melatonin treated middle-aged control rats displayed reduced concentrations of TGF-ß. Melatonin levels were significantly higher in all middle-aged rats treated animals. Reduced percentages of early and late thymocyte apoptosis was found for young and middle-aged melatonin supplemented rats. Finally, our results show a link between the therapeutic and biological effects of melatonin controlling steroidal hormones pathways as well as inflammatory mediators.


Assuntos
Citocinas/sangue , Melatonina/sangue , Envelhecimento/sangue , Envelhecimento/metabolismo , Aldosterona/sangue , Animais , Apoptose/efeitos dos fármacos , Corticosterona/sangue , Cortisona/sangue , Interleucina-1alfa/sangue , Interleucina-1beta/sangue , Masculino , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem , Timócitos/efeitos dos fármacos , Timócitos/metabolismo , Trypanosoma cruzi/patogenicidade
11.
PLoS One ; 15(8): e0238223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853260

RESUMO

Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions remain about the mechanisms underlying elevated blood pressure in full-term LBW infants. We previously reported that glucocorticoids increased miR-449a expression, and increased miR-449a expression suppressed Crhr1 expression and caused negative glucocorticoid feedback. Therefore, we conducted this study to clarify the involvement of pituitary miR-449a in the increase in blood pressure caused by higher glucocorticoids in LBW rats. We generated a fetal low-carbohydrate and calorie-restricted model rat (60% of standard chow), and some individuals showed postnatal growth failure caused by growth hormone receptor expression. Using this model, we examined how a high-fat diet (lard-based 45kcal% fat)-induced mismatch between prenatal and postnatal environments could elevate blood pressure after growth. Although LBW rats fed standard chow had slightly higher blood pressure than control rats, their blood pressure was significantly higher than controls when exposed to a high-fat diet. Observation of glomeruli subjected to periodic acid methenamine silver (PAM) staining showed no difference in number or size. Aortic and cardiac angiotensin II receptor expression was altered with compensatory responses. Blood aldosterone levels were not different between control and LBW rats, but blood corticosterone levels were significantly higher in the latter with high-fat diet exposure. Administration of metyrapone, a steroid synthesis inhibitor, reduced blood pressure to levels comparable to controls. We showed that high-fat diet exposure causes impairment of the pituitary glucocorticoid negative feedback via miR-449a. These results clarify that LBW rats have increased blood pressure due to high glucocorticoid levels when they are exposed to a high-fat diet. These findings suggest a new therapeutic target for hypertension of LBW individuals.


Assuntos
Pressão Sanguínea/fisiologia , Retroalimentação Fisiológica/fisiologia , Glucocorticoides/sangue , Doenças da Hipófise/sangue , Doenças da Hipófise/fisiopatologia , Hipófise/fisiologia , Animais , Peso ao Nascer/efeitos dos fármacos , Peso ao Nascer/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Corticosterona/sangue , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Recém-Nascido de Baixo Peso/sangue , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Masculino , Metirapona/uso terapêutico , Doenças da Hipófise/tratamento farmacológico , Hipófise/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Wistar
12.
PLoS One ; 15(7): e0236547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716920

RESUMO

Occlusal disharmony leads to morphological changes in the hippocampus and osteopenia of the lumbar vertebra and long bones in mice, and causes stress. Various types of stress are associated with increased incidence of cardiovascular disease, but the relationship between occlusal disharmony and cardiovascular disease remain poorly understood. Therefore, in this work, we examined the effects of occlusal disharmony on cardiac homeostasis in bite-opening (BO) mice, in which a 0.7 mm space was introduced by cementing a suitable applicance onto the mandibular incisior. We first examined the effects of BO on the level of serum corticosterone, a key biomarker for stress, and on heart rate variability at 14 days after BO treatment, compared with baseline. BO treatment increased serum corticosterone levels by approximately 3.6-fold and the low frequency/high frequency ratio, an index of sympathetic nervous activity, was significantly increased by approximately 4-fold by the BO treatment. We then examined the effects of BO treatment on cardiac homeostasis in mice treated or not treated with the non-selective ß-blocker propranolol for 2 weeks. Cardiac function was significantly decreased in the BO group compared to the control group, but propranolol ameliorated the dysfunction. Cardiac fibrosis, myocyte apoptosis and myocyte oxidative DNA damage were significantly increased in the BO group, but propranolol blocked these changes. The BO-induced cardiac dysfunction was associated with increased phospholamban phosphorylation at threonine-17 and serine-16, as well as inhibition of Akt/mTOR signaling and autophagic flux. These data suggest that occlusal disharmony might affect cardiac homeostasis via alteration of the autonomic nervous system.


Assuntos
Apoptose , Dano ao DNA , Miocárdio/patologia , Estresse Fisiológico , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Corticosterona/sangue , Eletrocardiografia , Fibrose , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
13.
Gen Comp Endocrinol ; 295: 113526, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32540490

RESUMO

Myopathies (Woody Breast (WB) and White Striping (WS)) of broiler chickens have been correlated with fast growth. Recent studies reported that localized hypoxia and metabolic impairment may involve in these myopathies of birds. In order to better understand the stress response mechanisms affecting myopathies of broilers, the aim of this study was to examine effects of WB and both WB/WS on stress hormone corticosterone (CORT) levels and expressional changes of stress response genes including glucocorticoid (GC) receptor (GR), 11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1), DNA methylation regulators (DNMTs), and arginine vasotocin receptor 1a and 1b (V1aR, V1bR). Results of radioimmunoassay showed that CORT levels of WB and WB/WS birds were significantly higher compared to Con (p < 0.05), however, the combination of WB/WS was not significantly higher than WB birds, implying that the effects of WB and WS on CORT are not synergistic. Hepatic GR expression of both WB and WB/WS birds were significantly higher compared to Con (p < 0.05). However, GR expression levels in breast muscle of both WB and WB/WS birds were decreased compared to Con (p < 0.05). Hepatic 11ß-HSD1 expression was increased only in WB/WS birds compared to Con birds with no significant difference between Con and WB birds. 11ß-HSD1 expression was decreased and increased in WB and WB/WS birds compared to Con, respectively, in breast muscle (p < 0.05). DNMT1 expression was significantly decreased in both muscle and liver of WB birds, and in muscle of WB/WS birds, but not in liver of WB/WS birds, indicating differential effects of WS on the epigenetical stress response of muscle and liver compared to WB. V1aR expression was significantly increased in muscle of WB birds, and in liver of WB/WS birds compared to Con birds (p < 0.05). V1bR was not changed in muscle and liver of WB birds compared to Con birds. Taken together, results suggest that GC-induced myopathies occur in fast-growing broiler chickens and circulating CORT level might be a significant biochemical marker of myopathies (WB and WS) of birds. In addition, chronic stress responses in breast muscle and tissue-specific epigenetic changes of stress response genes by DNMTs may play a critical role in the occurrence of myopathies.


Assuntos
Galinhas/fisiologia , Doenças Musculares/fisiopatologia , Doenças Musculares/veterinária , Estresse Fisiológico , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Animais , Peso Corporal , Galinhas/sangue , Galinhas/genética , Corticosterona/sangue , Metilação de DNA/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Fígado/metabolismo , Glândulas Mamárias Animais/metabolismo , Músculos/metabolismo , Doenças Musculares/sangue , Doenças Musculares/genética , Especificidade de Órgãos , Receptores de Glucocorticoides/metabolismo , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo
14.
Life Sci ; 256: 118018, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32598935

RESUMO

Aim While stress causes brain dysfunction, crocin (as an active component of saffron) and exercise (as part of a healthy lifestyle) improve stress-induced memory impairment. The present study investigated the protective effects of crocin administration, exercise, and crocin-accompanied exercise on neuronal excitability and long-term potentiation (LTP) at the CA1 of hippocampus as well as serum corticosterone and glucose levels in rats subjected to chronic unpredictable stress (CUS). MAIN METHODS: Forty-eight male Wistar rats were randomly allocated to six groups: Control, Sham, CUS, CUS-Crocin30, CUS-Exercise, and CUS-Crocin30-Exercise. The chronic unpredictable stress and treadmill running at 20-21 m/min were applied 2 h/day and 1 h/day, respectively, for 21 days. Crocin (30 mg/kg) was daily intraperitoneally injected to the rats. Electrophysiological variables were recorded from the CA1 of hippocampus. While corticosterone and glucose levels were also measured. KEY FINDINGS: CUS and CUS-Exercise significantly attenuated excitability and LTP. Compared to the CUS and CUS-Exercise treatments, CUS-Crocin30 and CUS-Crocin30-Exercise led to significant increases in slope and amplitude of field excitatory postsynaptic potential. The changes in serum corticosterone and glucose levels nearly matched the electrophysiological data. SIGNIFICANCE: CUS was found to be a highly destructive stress as it failed to allow exercises to edify the CUS-induced memory deficit. This is while crocin (as a herbal drug) was found more effective than exercise (as a daily routine) in remedying the CUS-induced memory deficit. Also, although the treatment with crocin-accompanied exercise did help recovery from the CUS-induced memory deficit, the interaction of crocin administration and exercise had no synergic effects; the protective effect observed was due to crocin administration rather than the exercise.


Assuntos
Carotenoides/farmacologia , Transtornos da Memória/terapia , Condicionamento Físico Animal/fisiologia , Estresse Psicológico/terapia , Animais , Glicemia/metabolismo , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Corticosterona/sangue , Modelos Animais de Doenças , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Transtornos da Memória/etiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Estresse Psicológico/complicações
15.
Anim Sci J ; 91(1): e13400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32512640

RESUMO

Biochemical and hematological examination of blood and individual assessment of the birds were performed in Lohman Brown laying hens at 45 weeks of age housed in different systems. The biochemical examination revealed higher (p < .01) corticosterone levels, creatine kinase, and aspartate aminotransferase activity and lower (p < .01) levels of lactate, triglycerides, albumin, calcium, and phosphorus in aviary hens compared to hens housed in furnished cages. Hematological examination of hens housed in aviaries revealed higher (p < .05) hematocrit, leukocytes, heterophils, eosinophils, basophils, monocytes, and H/L ratio. Furthermore, hens housed in aviaries had lower (p < .01) body weight than hens in furnished cages, they were worse feathered (p < .001), had more damaged combs (p < .05), and poorer physical condition (p < .01). In contrast, caged hens showed worse (p < .01) feather condition of the wings due to abrasion and claws due to overgrowth. The results have shown that the housing system has a significant impact on the internal environment and condition of birds and that housing in aviaries without taking into account the specifics of such housing may lead to significant stress and disturbance to the welfare of laying hens.


Assuntos
Criação de Animais Domésticos , Galinhas/metabolismo , Galinhas/fisiologia , Meio Ambiente , Abrigo para Animais , Bem-Estar do Animal , Animais , Peso Corporal , Corticosterona/sangue , Creatina Quinase/sangue , Plumas/patologia , Feminino , Oviposição
16.
Toxicol Lett ; 331: 167-177, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32535229

RESUMO

Prenatal ethanol exposure (PEE) could increase offspring's susceptibility to adult liver lipid-metabolism diseases. This study aimed to confirm intrauterine programming mechanism of glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis for liver dysfunction in offspring rats induced by PEE. The results showed that levels of hepatic IGF1, lipid metabolism-related enzymes (e.g. FASN and HMGCR) and serum phenotype (TG, TCH, HDL-C, and LDL-C) were low in fetal rats of PEE but high in adult offspring except for HDL-C, meanwhile, hepatic H3K9ac and expression levels of IGF1 were low in fetal rats but high in adult offspring. Furthermore, levels of serum corticosterone and hepatic glucocorticoid-activation system (mainly including expression of 11ß-HSD1, GR, and C/EBPα as well as 11ß-HSD1/11ß-HSD2 ratio) were high in fetal rats of PEE but low or unchanged in adult offspring. The adult F2 generation of PEE maintained the same GC-IGF1 axis programming alteration as the F1 generation despite gender differences. In vitro, cortisol was proved to activate hepatocyte glucocorticoid-activation system and decrease H3K9ac and expression levels of IGF1 by GR. Therefore, PEE has a long-term effect on the offspring's liver functional development, which may be mainly related to the epigenetic programming alteration of the GC-IGF1 axis mediated by the glucocorticoid-activation system.


Assuntos
Etanol/toxicidade , Glucocorticoides/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Peso Corporal , Corticosterona/sangue , Feminino , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/metabolismo , Células Hep G2 , Humanos , Lipídeos/sangue , Fígado/embriologia , Fígado/metabolismo , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Ratos Wistar , Transdução de Sinais
17.
Poult Sci ; 99(1): 546-554, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32416841

RESUMO

There is limited information on the effects of stress and/or physiological manipulation on either plasma concentrations of corticosterone (CORT) and/or heterophil: lymphocyte (H : L) ratios in turkeys. The present studies examine the effects of catching/transportation/lairage in a holding shed and shackling on plasma concentrations of CORT and H : L ratios in male market weight turkeys. Plasma concentrations of CORT were increased after transportation and lairage but not further elevated by shackling, irrespective of its duration up to 240 s. In one study, there were increased H : L ratios following catching/placing birds into transportation cages/transportation/lairage. In one study, H : L ratios declined following shackling. It is concluded that while moving turkeys from the farm to immediately before the shackling line is stressful, shackling for up to 4 min was not perceived as more stressful in turkeys. There were also differences between farms/houses for both plasma concentrations of CORT and H : L ratios.


Assuntos
Criação de Animais Domésticos , Corticosterona/sangue , Granulócitos/metabolismo , Linfócitos/metabolismo , Transportes , Perus/sangue , Criação de Animais Domésticos/métodos , Animais , Masculino , Estresse Fisiológico
18.
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
19.
Pharm Res ; 37(5): 87, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32356106

RESUMO

PURPOSE: Different anesthetic regimens are used during single pass intestinal perfusion (SPIP) experiments for the study of intestinal drug absorption in rats. We examined the ketamine/xylazine anesthetic combination to evaluate its influence on drug absorption compared to older regimens. Additionally, we examined whether supplementary analgesia has any effect on drug absorption and the effect of the different anesthetic regimens on induction time and stress response. METHODS: Rats were anesthetized using four different anesthetic regimens; ketamine/midazolam, pentobarbital, ketamine/xylazine and ketamine/xylazine/butorphanol. Three model drugs were administered to rat intestines and Peff was calculated. Stress response was evaluated by quantifying blood corticosterone levels and induction time was recorded. RESULTS: We found absorption under pentobarbital to be higher or similar to absorption under ketamine/midazolam. These results partly correlate with past literature data. Ketamine/xylazine was found to give similar or higher Peff compared to pentobarbital and ketamine/midazolam. Addition of butorphanol did not affect absorption and reduced induction time and stress. CONCLUSIONS: In studies of intestinal drug absorption, the ketamine/xylazine combination is superior to other anesthetic regimens as it is more convenient and seems to affect absorption to a lesser extent. Addition of butorphanol is highly recommended as it did not affect absorption but led to a more effective and less stress inducing experiment.


Assuntos
Anestésicos/administração & dosagem , Anestésicos/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Anestesia , Animais , Butorfanol , Corticosterona/sangue , Ketamina , Masculino , Midazolam , Pentobarbital , Ratos , Ratos Sprague-Dawley , Xilazina
20.
Int J Mol Sci ; 21(6)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32244957

RESUMO

Glucocorticoids are crucial for stress-coping, resilience, and adaptation. However, if the stress hormones become dysregulated, the vulnerability to stress-related diseases is enhanced. In this brief review, we discuss the role of glucocorticoids in the pathogenesis of neurodegenerative disorders in both human and animal models, and focus in particular on amyotrophic lateral sclerosis (ALS). For this purpose, we used the Wobbler animal model, which mimics much of the pathology of ALS including a dysfunctional hypothalamic-pituitary-adrenal axis. We discuss recent studies that demonstrated that the pathological cascade characteristic for motoneuron degeneration of ALS is mimicked in the genetically selected Wobbler mouse and can be attenuated by treatment with the selective glucocorticoid receptor antagonist (GRA) CORT113176. In long-term treatment (3 weeks) GRA attenuated progression of the behavioral, inflammatory, excitatory, and cell-death-signaling pathways while increasing the survival signal of serine-threonine kinase (pAkt). The action mechanism of the GRA may be either by interfering with GR deactivation or by restoring the balance between pro- and anti-inflammatory signaling pathways driven by the complementary mineralocorticoid receptor (MR)- and GR-mediated actions of corticosterone. Accordingly, GR antagonism may have clinical relevance for the treatment of neurodegenerative diseases.


Assuntos
Doenças Neurodegenerativas/tratamento farmacológico , Receptores de Glucocorticoides/metabolismo , Animais , Corticosterona/sangue , Corticosterona/química , Modelos Animais de Doenças , Humanos , Inflamação/sangue , Inflamação/complicações , Modelos Biológicos , Doenças Neurodegenerativas/sangue , Receptores de Glucocorticoides/antagonistas & inibidores
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