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1.
Proc Biol Sci ; 287(1929): 20200842, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32546100

RESUMO

The emergency life-history stage (ELHS) can be divided into two subcategories that describe distinct, coordinated responses to disease- or non-disease-related physiological challenges. Whether an individual can simultaneously express aspects of both subcategories when faced with multiple challenges is poorly understood. Emergency life-history theory suggests that disease- and non-disease-related responses are coordinated at the level of the whole organism and therefore cannot be expressed simultaneously. However, the reactive scope and physiological regulatory network models suggest that traits can be independently regulated, allowing for components of both disease- and non-disease-related responses to be simultaneously expressed within a single organism. To test these ideas experimentally, we subjected female zebra finches to food deprivation, an immune challenge, both, or neither, and measured a suite of behavioural and physiological traits involved in the ELHS. We examined whether the trait values expressed by birds experiencing simultaneous challenges resembled trait values of birds experiencing a single challenge or if birds could express a mixture of trait values concurrently. We find that birds can respond to simultaneous challenges by regulating components of the behavioural and immune responses independently of one another. Modularity within these physio-behavioural networks adds additional dimensions to how we evaluate the intensity or quality of an ELHS. Whether modularity provides fitness advantages or costs in nature remains to be determined.


Assuntos
Tentilhões/fisiologia , Animais , Corticosterona , Feminino , Privação de Alimentos , Comportamento de Doença , Estágios do Ciclo de Vida , Masculino
2.
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
3.
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
4.
Proc Biol Sci ; 287(1928): 20192952, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32517617

RESUMO

We investigated the effects of exposure at ecologically relevant levels of dim light at night (dLAN) on sleep and the 24 h hypothalamic expression pattern of genes involved in the circadian timing (per2, bmal1, reverb-ß, cry1, ror-α, clock) and sleep regulatory pathways (cytokines: tlr4, tnf-α, il-1ß, nos; Ca2+-dependent pathway: camk2, sik3, nr3a; cholinergic receptor, achm3) in diurnal female zebra finches. Birds were exposed to 12 h light (150 lux) coupled with 12 h of absolute darkness or of 5 lux dim light for three weeks. dLAN fragmented the nocturnal sleep in reduced bouts, and caused sleep loss as evidenced by reduced plasma oxalate levels. Under dLAN, the 24 h rhythm of per2, but not bmal1 or reverb-ß, showed a reduced amplitude and altered peak expression time; however, clock, ror-α and cry1 expressions showed an abolition of the 24 h rhythm. Decreased tlr4, il-1ß and nos, and the lack of diurnal difference in achm3 messenger RNA levels suggested an attenuated inhibition of the arousal system (hence, awake state promotion) under dLAN. Similarly, changes in camk2, sik3 and nr3a expressions suggested dLAN-effects on Ca2+-dependent sleep-inducing pathways. These results demonstrate dLAN-induced negative effects on sleep and associated hypothalamic molecular pathways, and provide insights into health risks of illuminated night exposures to diurnal animals.


Assuntos
Ritmo Circadiano/fisiologia , Tentilhões/fisiologia , Fotoperíodo , Sono/fisiologia , Animais , Corticosterona , Feminino , Expressão Gênica , Hipotálamo , Masculino
5.
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
6.
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
7.
Nat Commun ; 11(1): 2221, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376858

RESUMO

Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population. Such specificity is preferential to connections made by dmPFC, caused by enhanced presynaptic glutamate release, and highly correlated with the increased anxiety-like behavior in stressed mice. Importantly, low-frequency optogenetic stimulation of dmPFC afferents in BLA normalizes the enhanced prefrontal glutamate release onto dmPFC→BLA PNs and lastingly attenuates CRS-induced increase of anxiety-like behavior. Our findings thus reveal a target cell-based dysregulation of mPFC-to-amygdala transmission for stress-induced anxiety.


Assuntos
Tonsila do Cerebelo/fisiologia , Ansiedade/fisiopatologia , Ácido Glutâmico/metabolismo , Vias Neurais/fisiologia , Córtex Pré-Frontal/fisiologia , Estresse Psicológico , Animais , Ansiedade/metabolismo , Complexo Nuclear Basolateral da Amígdala/fisiologia , Corticosterona/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Optogenética , Restrição Física
8.
Proc Biol Sci ; 287(1926): 20200062, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32370671

RESUMO

The stress-induced susceptibility hypothesis, which predicts chronic stress weakens immune defences, was proposed to explain increasing infectious disease-related mass mortality and population declines. Previous work characterized wetland salinization as a chronic stressor to larval amphibian populations. Thus, we combined field observations with experimental exposures quantifying epidemiological parameters to test the role of salinity stress in the occurrence of ranavirus-associated mass mortality events. Despite ubiquitous pathogen presence (94%), populations exposed to salt runoff had slightly more frequent ranavirus related mass mortality events, more lethal infections, and 117-times greater pathogen environmental DNA. Experimental exposure to chronic elevated salinity (0.8-1.6 g l-1 Cl-) reduced tolerance to infection, causing greater mortality at lower doses. We found a strong negative relationship between splenocyte proliferation and corticosterone in ranavirus-infected larvae at a moderate elevation of salinity, supporting glucocorticoid-medicated immunosuppression, but not at high salinity. Salinity alone reduced proliferation further at similar corticosterone levels and infection intensities. Finally, larvae raised in elevated salinity had 10 times more intense infections and shed five times as much virus with similar viral decay rates, suggesting increased transmission. Our findings illustrate how a small change in habitat quality leads to more lethal infections and potentially greater transmission efficiency, increasing the severity of ranavirus epidemics.


Assuntos
Anfíbios/virologia , Infecções por Vírus de DNA/veterinária , Ranavirus , Anfíbios/fisiologia , Animais , Corticosterona/metabolismo , Infecções por Vírus de DNA/epidemiologia , Epidemias , Estresse Salino/fisiologia
9.
PLoS One ; 15(5): e0232120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407351

RESUMO

Decades of work indicate that female birds can control their offspring sex ratios in response to environmental and social cues. In laying hens, hormones administered immediately prior to sex chromosome segregation can exert sex ratio skews, indicating that these hormones may act directly on the germinal disc to influence which sex chromosome is retained in the oocyte and which is discarded into an unfertilizable polar body. We aimed to uncover the gene pathways involved in this process by testing whether treatments with testosterone or corticosterone that were previously shown to influence sex ratios elicit changes in the expression of genes and/or gene pathways involved in the process of meiotic segregation. We injected laying hens with testosterone, corticosterone, or control oil 5h prior to ovulation and collected germinal discs from the F1 preovulatory follicle in each hen 1.5h after injection. We used RNA-sequencing (RNA-seq) followed by DESeq2 and gene set enrichment analyses to identify genes and gene pathways that were differentially expressed between germinal discs of control and hormone-treated hens. Corticosterone treatment triggered downregulation of 13 individual genes, as well as enrichment of gene sets related to meiotic spindle organization and chromosome segregation, and additional gene sets that function in ion transport. Testosterone treatment triggered upregulation of one gene, and enrichment of one gene set that functions in nuclear chromosome segregation. This work indicates that corticosterone can be a potent regulator of meiotic processes and provides potential gene targets on which corticosterone and/or testosterone may act to influence offspring sex ratios in birds.


Assuntos
Corticosterona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Meiose/efeitos dos fármacos , Meiose/genética , Folículo Ovariano/citologia , Ovulação , Testosterona/farmacologia , Animais , Galinhas , Feminino , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia
10.
Life Sci ; 251: 117597, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32243926

RESUMO

Stress during pregnancy adversely affects foetal development and leads to later behavioural outcomes in offspring. Preclinical studies have reported conflicting effects of prenatal stress on depression-related symptoms in rodent offspring. This study aimed to study the combined effect of strain and sex on prenatal stress outcomes in a single study. To this end, male and female offspring from outbred Wistar and inbred Lewis rats, and outbred NMRI and inbred C57BL6 mice were compared. As outcomes we focussed on depression-related behaviour and related molecular and neurochemical parameters. Prenatally stressed and non-stressed offspring were subjected to the sucrose preference, novelty-suppressed feeding, tail suspension, and forced swim tests. We measured basal and stress-induced corticosterone levels in the serum, and brain-derived-neurotrophic-factor (BDNF), interleukin-1ß, tumor necrosis factor-α, glutamate and serotonin in the brain to determine changes in hypothalamic-pituitary-adrenal-(HPA)-axis function, neuroplasticity, neuroinflammation, and neurotransmission. Our findings revealed that prenatal stress increases depression-like behaviour, HPA-axis (re) activity, pro-inflammatory cytokines and glutamate levels, and decreases BDNF and serotonin levels in a strain and sex-dependent manner in rodent offspring. Overall, male and female Lewis rats, female Wistar rats, male NMRI mice and female C57BL6 mice were found to be most responsive to prenatal stress. Based on these results, we conclude that genetic background and sex contribute to the great diversity in the effects of prenatal maternal stress in rodents.


Assuntos
Depressão/psicologia , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estresse Psicológico/psicologia , Animais , Encéfalo/metabolismo , Corticosterona/sangue , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Ratos , Ratos Endogâmicos Lew , Ratos Wistar , Fatores Sexuais , Especificidade da Espécie
12.
Poult Sci ; 99(3): 1618-1627, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32111329

RESUMO

Early-life exposure to stressors can shape the phenotype of the offspring resulting in changes that may affect their prehatch and posthatch development. This can be modeled indirectly through maternal exposure to stressors (natural model) or by offspring exposure to stress hormones (pharmacological model). In this study, both models were used to investigate the effects of genetic line on hatchability, late embryonic mortality, sex ratio, and body weight until 17 wk of age. To form the parent stock, fertilized eggs of 4 commercial genetic lines - two brown (brown 1 and 2), two white (white 1 and 2), and a pure line White Leghorn - were incubated, hatched, and housed identically in 4 flocks of 27 birds (24 females and 3 males) per strain. Each strain was equally separated into 2 groups: "maternal stress," where hens were subjected to a series of acute psychological stressors (e.g., physical restraint, transportation) for 8 D before egg collection, and "control," where hens received routine husbandry. At 3 maternal ages, fertile eggs from both treatments were collected, and additional eggs from the control group were injected with corticosterone (10 ng/mL egg content) ("CORT"). A "vehicle" treatment was included to account for effects of egg manipulation. Each maternal age comprised a replicate over time. Eggs were incubated and hatched, and the offspring (N = 1,919) were brooded until 17 wk under identical conditions. The results show that prenatal stress interacted with strain to decrease embryonic survival and growth. Among all strains, brown 2 was consistently the most affected line in both prehatch and posthatch development. Our study shows that embryonic survival and offspring growth are mostly affected by the pharmacological model and that strain differences may increase susceptibility to prenatal stress. Moreover, it suggests that the natural stressor model may be useful for quantifying the response of the mother to stressors, whereas the pharmacological model may be useful for quantifying the response of the embryo to increased levels of corticosterone.


Assuntos
Galinhas/crescimento & desenvolvimento , Galinhas/genética , Corticosterona/farmacologia , Estresse Psicológico , Criação de Animais Domésticos/métodos , Animais , Peso Corporal , Embrião de Galinha , Corticosterona/administração & dosagem , Feminino , Injeções/veterinária , Masculino , Exposição Materna , Óvulo , Restrição Física/efeitos adversos , Razão de Masculinidade , Especificidade da Espécie
13.
Proc Natl Acad Sci U S A ; 117(14): 8104-8114, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32193346

RESUMO

There is extensive evidence that glucocorticoid hormones enhance memory consolidation, helping to ensure that emotionally significant events are well remembered. Prior findings suggest that the anteroventral region of bed nuclei of the stria terminalis (avBST) regulates glucocorticoid release, suggesting the potential for avBST activity to influence memory consolidation following an emotionally arousing learning event. To investigate this issue, male Sprague-Dawley rats underwent inhibitory avoidance training and repeated measurement of stress hormones, immediately followed by optogenetic manipulations of either the avBST or its projections to downstream regions, and 48 h later were tested for retention. The results indicate that avBST inhibition augmented posttraining pituitary-adrenal output and enhanced the memory for inhibitory avoidance training. Pretreatment with a glucocorticoid synthesis inhibitor blocked the memory enhancement as well as the potentiated corticosterone response, indicating the dependence of the memory enhancement on glucocorticoid release during the immediate posttraining period. In contrast, posttraining avBST stimulation decreased retention yet had no effect on stress hormonal output. Subsequent experiments revealed that inhibition of avBST input to the paraventricular hypothalamus enhanced stress hormonal output and subsequent retention, whereas stimulation did not affect either. Conversely, stimulation-but not inhibition-of avBST input to the ventrolateral periaqueductal gray impaired consolidation, whereas neither manipulation affected glucocorticoid secretion. These findings indicate that divergent pathways from the avBST are responsible for the mnemonic effects of avBST inhibition versus stimulation and do so via glucocorticoid-dependent and -independent mechanisms, respectively.


Assuntos
Aprendizagem da Esquiva/fisiologia , Glucocorticoides/metabolismo , Consolidação da Memória/fisiologia , Núcleos Septais/fisiologia , Hormônio Adrenocorticotrópico/análise , Hormônio Adrenocorticotrópico/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Corticosterona/análise , Corticosterona/metabolismo , Glucocorticoides/análise , Glucocorticoides/antagonistas & inibidores , Masculino , Consolidação da Memória/efeitos dos fármacos , Metirapona/administração & dosagem , Modelos Animais , Vias Neurais/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Optogenética , Núcleo Hipotalâmico Paraventricular/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de Glucocorticoides/metabolismo , Núcleos Septais/citologia
14.
Life Sci ; 250: 117545, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32173313

RESUMO

AIMS: Chronic stress leads to the development of male sexual problems such as ejaculatory dysfunctions. The rhythmic contractions of vas deferens (VD) play an important role on the ejaculatory process. In the current study, we investigated whether infliximab (IFX) treatment has any beneficial effects on possible alterations in contractility of VD obtained from rats exposed to unpredictable chronic mild stress (UCMS). MATERIALS AND METHODS: The rats were randomly divided into four groups: control, control+IFX, UCMS and UCMS+IFX. IFX (5 mg/kg/week, i.p.) was administrated for 5 weeks during UCMS period. Depressive like-behaviors were evaluated using locomotor activity, forced swimming and sucrose consumption and preference tests. The blood was collected for serum biochemical determinations. VD tissues were harvested for functional studies and, measurements of oxidative stress, inflammatory and apoptotic biomarkers. KEY FINDINGS: We observed increased serum concentration of corticosterone and depressive-like behaviors in rats exposed to UCMS. In VD tissues of UCMS-exposed rats, noradrenaline- and adenosine triphosphate (ATP)-induced contractile responses significantly enhanced and electrical field stimulation (EFS)-induced contractile responses markedly decreased. UCMS exposure induced inflammation, oxidative stress and apoptosis in VD. However, IFX treatment significantly improved all the aforementioned parameters. SIGNIFICANCE: The results of the present study revealed that chronic stress-induced depression caused VD dysfunction by promoting inflammation and oxidative stress in VD. IFX protected against VD dysfunction through its anti-inflammatory and antioxidant effects.


Assuntos
Infliximab/farmacologia , Estresse Oxidativo , Estresse Fisiológico , Ducto Deferente/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Corticosterona/sangue , Depressão/tratamento farmacológico , Relação Dose-Resposta a Droga , Ejaculação/efeitos dos fármacos , Campos Eletromagnéticos , Glutationa/metabolismo , Inflamação/sangue , Peroxidação de Lipídeos , Masculino , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Sacarose/química , Superóxido Dismutase/metabolismo
15.
Eur J Endocrinol ; 182(5): 459-471, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32130202

RESUMO

Objective: To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men. Design: Cross-sectional study. Methods: Three hundred and fifteen adults, drug-free and apparently healthy men underwent clinical and biochemical evaluation. Thirteen steroids were measured by LC-MS/MS and compared among men with increasing BMI. Moreover, the independent impact of age, BMI and metabolic parameters on steroid levels was estimated. Upper and lower reference limits were generated in steroid-specific reference sub-cohorts and compared with dysmetabolic sub-cohorts. Results: We observed lower steroid precursors and testosterone and increase in estrone levels in men with higher BMI ranges. By multivariate analysis, 17-hydroxyprogesterone and dihydrotestosterone decreased with BMI, while cortisol decreased with waist circumference. Estrone increased with BMI and systolic blood pressure. Testosterone decreased with worsening insulin resistance. 17-hydroxypregnenolone and corticosterone decreased with increasing total/HDL-cholesterol ratio. Age-related reference intervals were estimated for 17-hydroxypregnenolone, DHEA, 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol, cortisol and androstenedione, while age-independent reference intervals were estimated for progesterone, 11-deoxycorticosterone, testosterone, dihydrotestosterone, estrone and estradiol. Testosterone lower limit was 2.29 nmol/L lower (P = 0.007) in insulin resistant vs insulin sensitive men. Furthermore, the upper limits for dihydrotestosterone (-0.34 nmol/L, P = 0.045), cortisol (-87 nmol/L, P = 0.045-0.002) and corticosterone (-10.1 nmol/L, P = 0.048-0.016) were lower in overweight/obese, in abdominal obese and in dyslipidaemic subjects compared to reference sub-cohorts, respectively. Conclusions: Obesity and mild unmedicated metabolic risk factors alter the circulating steroid profile and bias the estimation of reference limits for testosterone, dihydrotestosterone, cortisol and corticosterone. Applying age-dependent reference intervals is mandatory for steroid precursors and corticosteroids.


Assuntos
Peso Corporal/fisiologia , 17-alfa-Hidroxiprogesterona/sangue , Fatores Etários , Androstenodiona/sangue , Índice de Massa Corporal , Cromatografia Líquida , Corticosterona/sangue , Cortodoxona/sangue , Estudos Transversais , Desidroepiandrosterona/sangue , Di-Hidrotestosterona/sangue , Humanos , Hidrocortisona/sangue , Masculino , Análise Multivariada , Obesidade/sangue , Sobrepeso/sangue , Fatores de Risco , Espectrometria de Massas em Tandem
16.
Nat Commun ; 11(1): 1119, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111822

RESUMO

The roots of psychopathology frequently take shape during infancy in the context of parent-infant interactions and adversity. Yet, neurobiological mechanisms linking these processes during infancy remain elusive. Here, using responses to attachment figures among infants who experienced adversity as a benchmark, we assessed rat pup cortical local field potentials (LFPs) and behaviors exposed to adversity in response to maternal rough and nurturing handling by examining its impact on pup separation-reunion with the mother. We show that during adversity, pup cortical LFP dynamic range decreased during nurturing maternal behaviors, but was minimally impacted by rough handling. During reunion, adversity-experiencing pups showed aberrant interactions with mother and blunted cortical LFP. Blocking pup stress hormone during either adversity or reunion restored typical behavior, LFP power, and cross-frequency coupling. This translational approach suggests adversity-rearing produces a stress-induced aberrant neurobehavioral processing of the mother, which can be used as an early biomarker of later-life pathology.


Assuntos
Animais Recém-Nascidos , Encéfalo/fisiologia , Comportamento Materno/fisiologia , Apego ao Objeto , Estresse Psicológico/fisiopatologia , Animais , Animais Recém-Nascidos/fisiologia , Animais Recém-Nascidos/psicologia , Ansiedade de Separação/sangue , Ansiedade de Separação/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Encéfalo/efeitos dos fármacos , Corticosterona/antagonistas & inibidores , Corticosterona/sangue , Feminino , Masculino , Relações Mãe-Filho , Mães , Ratos , Estresse Psicológico/sangue
17.
Invest Ophthalmol Vis Sci ; 61(3): 26, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32182332

RESUMO

Purpose: Elevated IOP can cause the development of glaucoma. The circadian rhythm of IOP depends on the dynamics of the aqueous humor and is synchronized with the circadian rhythm pacemaker, that is, the suprachiasmatic nucleus. The suprachiasmatic nucleus resets peripheral clocks via sympathetic nerves or adrenal glucocorticoids. However, the detailed mechanisms underlying IOP rhythmicity remain unclear. The purpose of this study was to verify this regulatory pathway. Methods: Adrenalectomy and/or superior cervical ganglionectomy were performed in C57BL/6J mice. Their IOP rhythms were measured under light/dark cycle and constant dark conditions. Ocular administration of corticosterone or norepinephrine was also performed. Localization of adrenergic receptors, glucocorticoid receptors, and clock proteins Bmal1 and Per1 were analyzed using immunohistochemistry. Period2::luciferase rhythms in the cultured iris/ciliary bodies of adrenalectomized and/or superior cervical ganglionectomized mice were monitored to evaluate the effect of the procedures on the local clock. The IOP rhythm of retina and ciliary epithelium-specific Bmal1 knockout mice were measured to determine the significance of the local clock. Results: Adrenalectomy and superior cervical ganglionectomy disrupted IOP rhythms and the circadian clock in the iris/ciliary body cultures. Instillation of corticosterone and norepinephrine restored the IOP rhythm. ß2-Adrenergic receptors, glucocorticoid receptors, and clock proteins were strongly expressed within the nonpigmented epithelia of the ciliary body. However, tissue-specific Bmal1 knock-out mice maintained their IOP rhythm. Conclusions: These findings suggest direct driving of the IOP rhythm by the suprachiasmatic nucleus, via the dual corticosterone and norepinephrine pathway, but not the ciliary clock, which may be useful for chronotherapy of glaucoma.


Assuntos
Ritmo Circadiano/fisiologia , Corticosterona/farmacologia , Pressão Intraocular/fisiologia , Norepinefrina/farmacologia , Sistema Nervoso Simpático/fisiologia , Fatores de Transcrição ARNTL/metabolismo , Administração Oftálmica , Adrenalectomia , Animais , Células Cultivadas , Corpo Ciliar/efeitos dos fármacos , Corpo Ciliar/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Ganglionectomia , Imuno-Histoquímica , Iris/efeitos dos fármacos , Iris/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Circadianas Period/metabolismo , Fotoperíodo , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Glucocorticoides/metabolismo , Gânglio Cervical Superior/cirurgia , Tonometria Ocular
18.
Sci Total Environ ; 721: 137332, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32169634

RESUMO

Urbanization changes the landscape structure and ecological processes of natural habitats. While urban areas expose animal communities to novel challenges, they may also provide more stable environments in which environmental fluctuations are buffered. Species´ ecology and physiology may determine their capacity to cope with the city life. However, the physiological mechanisms underlying organismal responses to urbanization, and whether different physiological systems are equally affected by urban environments remain poorly understood. This severely limits our capacity to predict the impact of anthropogenic habitats on wild populations. In this study, we measured indicators of physiological stress at the endocrine, immune and cellular level (feather corticosterone levels, heterophil to lymphocyte ratio, and heat-shock proteins) in urban and non-urban European blackbirds (Turdus merula) across 10 European populations. Among the three variables, we found consistent differences in feather corticosterone, which was higher in non-urban habitats. This effect seems to be dependent on sex, being greater in males. In contrast, we found no significant differences between urban and non-urban habitats in the two other physiological indicators. The discrepancy between these different measurements of physiological stress highlights the importance of including multiple physiological variables to understand the impact of urbanization on species' physiology. Overall, our findings suggest that adult European blackbirds living in urban and non-urban habitats do not differ in terms of physiological stress at an organismal level. Furthermore, we found large differences among populations on the strength and direction of the urbanization effect, which illustrates the relevance of spatial replication when investigating urban-induced physiological responses.


Assuntos
Aves Canoras , Urbanização , Animais , Cidades , Corticosterona , Ecossistema , Masculino , Estresse Fisiológico
19.
Nat Commun ; 11(1): 1453, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193397

RESUMO

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Neurônios GABAérgicos/metabolismo , Núcleo Supraquiasmático/fisiologia , Peptídeo Intestinal Vasoativo/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Bicuculina/farmacologia , Channelrhodopsins/química , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Relógios Circadianos/efeitos dos fármacos , Corticosterona/sangue , Corticosterona/metabolismo , Eletrodos Implantados , Feminino , Antagonistas de Receptores de GABA-A/farmacologia , Neurônios GABAérgicos/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Modelos Animais , Núcleo Supraquiasmático/citologia , Peptídeo Intestinal Vasoativo/antagonistas & inibidores , Peptídeo Intestinal Vasoativo/genética
20.
Poult Sci ; 99(2): 829-838, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32029165

RESUMO

Broiler breeders are commonly feed restricted using some variation of skip-a-day feeding to prevent excessive body weight (BW) gain and poor flock uniformity that results in lower production levels. However, the level of feed restriction has increased leading to negative effects on broiler breeder welfare. Research needs to be conducted to evaluate alternative feeding programs to diminish the negative impact of restricted feeding on bird welfare. This research examined pullets that were fed soybean hulls (alternate day feeding, ATD) on the off day of a traditional skip-a-day feeding program in comparison to the standard skip-a-day program (SAD). The 2 dietary feeding treatments each had 3 replicate pens of 210 pullets each and were fed from wk 5 to 21 of age. Nitrogen-corrected true metabolizable energy and digestible amino acid coefficients of soybean hulls were determined. Body weight in the ATD feed program was significantly higher (P < 0.001) than the birds on the SAD feed program until 16 wk of age. Feed allocations for the SAD feeding program was increased at 11 wk of age to achieve similar BW prior to photo stimulation. The ATD feed program significantly improved BW uniformity of the birds for weeks 8, 12, 16, and 20. Hens fed on the SAD feed program had a lower mean egg production than the hens fed on the ATD program. There were significant differences on plasma corticosterone concentrations between the feeding days (24 or 48 h after feeding) in both feed programs. There was a shift in the behavior of the birds with significant differences in the feeding, foraging, and comfort behaviors between the feeding programs on the same feed day. Overall, feeding the ATD females soybean hulls on the off feed day improved the BW uniformity and egg production, but further research will be needed to determine potential differences in nutrient utilization or behavior of the pullets that positively impacted this flock performance.


Assuntos
Criação de Animais Domésticos/métodos , Bem-Estar do Animal , Galinhas/fisiologia , Corticosterona/sangue , Comportamento Alimentar , Frustração , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/sangue , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Distribuição Aleatória , Sementes/química , Soja/química
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