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1.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540792

RESUMO

The skin barrier consists of mucus, primarily comprising highly glycosylated mucins, and the epithelium. Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function. We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress. Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment. Blood parameters indicated primary and secondary stress responses at both sampling points. At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01). Liquid chromatography-mass spectrometry revealed 81 O-glycan structures from the skin. Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures. Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress. Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.


Assuntos
Aglomeração , Mucinas/metabolismo , Muco/química , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/metabolismo , Salmo salar/metabolismo , Absorção Cutânea/fisiologia , Pele/metabolismo , Estresse Fisiológico/fisiologia , Estresse Psicológico/metabolismo , Animais , Biomarcadores , Cromatografia Líquida , Aglomeração/psicologia , Glicosilação , Hidrocortisona/sangue , Manitol/farmacocinética , Espectrometria de Massas , Mucinas/isolamento & purificação , Muco/metabolismo , Ácido N-Acetilneuramínico/isolamento & purificação , Oxigênio/análise , Polissacarídeos/isolamento & purificação , Processamento de Proteína Pós-Traducional , Salmo salar/sangue , Pele/ultraestrutura , Temperatura , Qualidade da Água
3.
PLoS One ; 15(12): e0225023, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33326450

RESUMO

Dog training methods range broadly from those using mostly positive punishment and negative reinforcement (aversive-based) to those using primarily positive reinforcement (reward-based). Although aversive-based training has been strongly criticized for negatively affecting dog welfare, there is no comprehensive research focusing on companion dogs and mainstream techniques, and most studies rely on owner-reported assessment of training methods and dog behavior. The aim of the present study was to evaluate the effects of aversive- and reward-based training methods on companion dog welfare within and outside the training context. Ninety-two companion dogs were recruited from three reward-based schools (Group Reward, n = 42), and from four aversive-based schools, two using low proportions of aversive-based methods (Group Mixed, n = 22) and two using high proportions of aversive-based methods (Group Aversive, n = 28). For evaluating welfare during training, dogs were video recorded for three sessions and six saliva samples were collected, three at home (baseline levels) and three after training (post-training levels). Video recordings were used to examine the frequency of stress-related behaviors (e.g., lip lick, yawn) and the overall behavioral state of the dog (e.g., tense, relaxed), and saliva samples were analyzed for cortisol concentration. For evaluating welfare outside the training context, dogs participated in a cognitive bias task. Results showed that dogs from Group Aversive displayed more stress-related behaviors, were more frequently in tense and low behavioral states and panted more during training, and exhibited higher post-training increases in cortisol levels than dogs from Group Reward. Additionally, dogs from Group Aversive were more 'pessimistic' in the cognitive bias task than dogs from Group Reward. Dogs from Group Mixed displayed more stress-related behaviors, were more frequently in tense states and panted more during training than dogs from Group Reward. Finally, although Groups Mixed and Aversive did not differ in their performance in the cognitive bias task nor in cortisol levels, the former displayed more stress-related behaviors and was more frequently in tense and low behavioral states. These findings indicate that aversive-based training methods, especially if used in high proportions, compromise the welfare of companion dogs both within and outside the training context.


Assuntos
Animais de Estimação/psicologia , Reforço Psicológico , Afeto/fisiologia , Animais , Comportamento Animal/fisiologia , Condicionamento Psicológico/fisiologia , Cães , Humanos , Hidrocortisona/análise , Masculino , Punição/psicologia , Recompensa , Saliva/química , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Inquéritos e Questionários , Gravação em Vídeo
4.
Int J Mol Sci ; 21(24)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348553

RESUMO

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity.


Assuntos
Cicloexenos/administração & dosagem , Dopamina/metabolismo , Hipocampo/metabolismo , Humulus/química , Extratos Vegetais/administração & dosagem , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Terpenos/administração & dosagem , Sintomas Afetivos/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Cicloexenos/química , Modelos Animais de Doenças , Isomerismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Terpenos/química
5.
Rev. neurol. (Ed. impr.) ; 71(12): 460-466, 16 dic., 2020.
Artigo em Espanhol | IBECS | ID: ibc-199340

RESUMO

INTRODUCCIÓN: Entre los mediadores químicos que modulan el eje intestino-cerebro debe incluirse el sistema orexinérgico, ya que la orexina A (OXA) hipotalámica interviene en la motilidad y en la secreción gastrointestinal. También está presente en las células enteroendocrinas de la mucosa intestinal y en las neuronas aferentes primarias del plexo mientérico, y puede intervenir en la señalización intestino-cerebro. OBJETIVO: No se conoce con exactitud la fuente ni la señal que originan la liberación de OXA periférica, ni tampoco si actúa en los receptores orexinérgicos de los tejidos periféricos ante demandas fisiológicas o patológicas. Esta revisión intenta analizar estas cuestiones a la luz de nuevos datos que indican que la OXA en el eje intestino-cerebro puede tener funciones más allá de su participación en la homeostasis energética. DESARROLLO: La OXA en el sistema entérico protege de la inflamación sistémica y central, y en el hipotálamo orquesta numerosos efectos periféricos para suprimir la respuesta inflamatoria sistémica. Por ello, podría actuar como sustancia inmunomoduladora en inflamaciones crónicas o en enfermedades autoinmunitarias. La OXA también se relaciona con la respuesta de estrés, regulando las respuestas fisiológicas a estímulos emocionales o estresantes. CONCLUSIONES: Aunque la OXA tiene efectos antiinflamatorios y gastroprotectores de la mucosa intestinal, en procesos de inflamación crónica podría incrementar la respuesta a estímulos estresantes, tanto externos como internos, y exacerbar la inflamación gastrointestinal. Por ello, se han propuesto intervenciones farmacológicas sobre el sistema orexinérgico como tratamiento para enfermedades en las que la hipersensibilidad intestinal coexiste con pérdida de apetito, alteraciones del sueño, estrés y ansiedad


INTRODUCTION. The orexinergic system is one of the chemical mediators that modulate the gut-brain axis, given the involvement of hypothalamic orexin A (OXA) in gastrointestinal motility and secretion, and the presence of OXA in enteroendocrine cells of the intestinal mucosa and in primary afferent neurons of the mesenteric plexus, permitting its participation in gut-brain signaling. AIM. The source of OXA and the signal(s) triggering its peripheral release are not fully understood, and it is not known whether it acts on orexigenic receptors in peripheral tissues to meet physiological or pathological demands. The aim of this review is to address these questions in the light of new data indicating that OXA may have functions in the gut-brain axis that go beyond its participation in energy homeostasis. DEVELOPMENT. OXA in the enteric system protects against systemic and central inflammation, and hypothalamic OXA orchestrates numerous peripheral effects to suppress the systemic inflammatory response. For this reason, OXA may act as an immunomodulator in chronic inflammations or autoimmune diseases. OXA is also involved in the stress response, regulating physiological responses to emotional or stressful stimuli. CONCLUSIONS. OXA exerts anti-inflammatory and gastroprotective effects on the intestinal mucosa; however, it may increase the response to external and/or internal stress in individuals with chronic inflammation, exacerbating the gastrointestinal inflammation. Hence, pharmacologic interventions in the orexinergic system have been proposed to treat diseases in which intestinal hypersensitivity is combined with appetite loss, sleep disturbance, stress, and anxiety


Assuntos
Humanos , Orexinas/fisiologia , Trato Gastrointestinal/metabolismo , Sistema Imunitário/metabolismo , Estresse Psicológico/metabolismo , Neurônios/metabolismo , Orexinas/análise
6.
Artigo em Inglês | MEDLINE | ID: mdl-33115820

RESUMO

INTRODUCTION: The COVID-19 pandemic forced the Italian government to issue extremely restrictive measures on daily activities since 11 March 2020 ('lockdown'), which may have influenced the metabolic control of type 1 diabetes mellitus (T1D). The aims of the study were to investigate continuous glucose monitoring (CGM) metrics in children and adults with T1D during lockdown and to identify their potentially related factors. RESEARCH DESIGN AND METHODS: We enrolled 130 consecutive patients with T1D (30 children (≤12 years), 24 teenagers (13-17 years), and 76 adults (≥18 years)) using either Dexcom or FreeStyle LibreCGM>70% during the study period, without hybrid closed-loop insulin pump. CGM metrics during the 20 days before and the 20 days after lockdown were calculated. By telephonic contact, we performed validated physical activity and perceived stress questionnaires. RESULTS: In children, significantly lower glucose SD (SDglu) (p=0.029) and time below range (TBR)<54 mg/dL (TBR2) (p=0.029) were detected after lockdown. CGM metrics were comparable in teenagers before and during lockdown. After lockdown, adults improved significantly time in range (TIR) 70-180 mg/dL (p<0.001) and remaining metrics, except percent coefficient of variation and TBR2. In adults, considering the changes in SDglu and TIR occurred before and during lockdown, we identified a group with improved TIR and SDglu who performed more physical activity, one with improved glucose variability who was younger than the other patients, and one with worsened glucose variability who showed higher perceived stress than others. CONCLUSION: In patients with T1D during lockdown, CGM metrics mostly improved in children and adults, whereas it was unchanged in teenagers. In adults, age, physical activity, and perceived stress may be relevant contributing factors.


Assuntos
Glicemia/metabolismo , Controle de Doenças Transmissíveis , Infecções por Coronavirus , Diabetes Mellitus Tipo 1/metabolismo , Pandemias , Pneumonia Viral , Adolescente , Adulto , Betacoronavirus , Automonitorização da Glicemia , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Exercício Físico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Estresse Psicológico/metabolismo
7.
J Pharm Biomed Anal ; 191: 113604, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32957066

RESUMO

Stress and stress-related diseases are leading to drastic consequences in private and professional life. Therefore, the need for stress prevention strategies is of personal and economic interest. Especially during the recent period related to covid-19 outbreak and lock-down, an ongoing discussion of increasing stress etiology is reported. Biomarker analysis may help to assist diagnosis and classification of stress-related diseases and therefore support therapeutical decisions. Due to its non-invasive sampling, the analysis of saliva has become highly attractive compared to the detection methods in other specimen. This review article summarizes the status of research, innovative approaches, and trends. Scientific literature published since 2011 was excerpted with concentration on the detection of up to seven promising marker substances. Most often reported cortisol represents the currently best evaluated stress marker, while norepinephrine (noradrenaline) or its metabolite 3-methoxy-4-hydroxyphenylglycol is also a quite commonly considered stress marker. Other complementary stress marker candidates are testosterone, dehydroepiandrosterone (DHEA) and its sulfonated analogue DHEA-S, alpha-amylase, secretory immunoglobulin A, and chromogranin A. Several working groups are researching in the field of stress marker detection to develop reliable, fast, and affordable methods. Analytical methods reported mainly focused on immunological and electrochemical as well as chromatographic methods hyphenated to mass spectrometric detection to yield the required detection limits.


Assuntos
Biomarcadores/análise , Infecções por Coronavirus/metabolismo , Pandemias , Pneumonia Viral/metabolismo , Saliva/química , Estresse Psicológico/diagnóstico , Estresse Psicológico/metabolismo , Humanos , Manejo de Espécimes
8.
Subst Use Misuse ; 55(14): 2438-2442, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32957797

RESUMO

BACKGROUND: The overwhelming fatalities of the global COVID-19 Pandemic will have daunting epigenetic sequala that can translate into an array of mental health issues, including panic, phobia, health anxiety, sleep disturbances to dissociative like symptoms including suicide. Method: We searched PUBMED for articles listed using the search terms "COVID 19 Pandemic", COVID19 and genes," "stress and COVID 19", Stress and Social distancing: Results: Long-term social distancing may be neurologically harmful, the consequence of epigenetic insults to the gene encoding the primary receptor for SARS-CoV2, and COVID 19. The gene is Angiotensin I Converting-Enzyme 2 (ACE2). According to the multi-experiment matrix (MEM), the gene exhibiting the most statistically significant co-expression link to ACE2 is Dopa Decarboxylase (DDC). DDC is a crucial enzyme that participates in the synthesis of both dopamine and serotonin. SARS-CoV2-induced downregulation of ACE2 expression might reduce dopamine and serotonin synthesis, causing hypodopaminergia. Discussion: Indeed, added to the known reduced dopamine function during periods of stress, including social distancing the consequence being both genetic and epigenetic vulnerability to all Reward Deficiency Syndrome (RDS) addictive behaviors. Stress seen in PTSD can generate downstream alterations in immune functions by reducing methylation levels of immune-related genes. Conclusion: Mitigation of these effects by identifying subjects at risk and promoting dopaminergic homeostasis to help regulate stress-relative hypodopaminergia, attenuate fears, and prevent subsequent unwanted drug and non-drug RDS type addictive behaviors seems prudent.


Assuntos
Comportamento Aditivo/genética , Infecções por Coronavirus/metabolismo , Dopamina/metabolismo , Pneumonia Viral/metabolismo , Ansiedade/genética , Ansiedade/metabolismo , Comportamento Aditivo/metabolismo , Comportamento Aditivo/psicologia , Betacoronavirus , Infecções por Coronavirus/psicologia , Dopa Descarboxilase/genética , Dopa Descarboxilase/metabolismo , Regulação para Baixo , Epigênese Genética , Humanos , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/psicologia , Recompensa , Estresse Psicológico/genética , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/psicologia , Suicídio , Síndrome
9.
Anesth Analg ; 131(4): 1291-1299, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32925350

RESUMO

BACKGROUND: Neonatal exposure to sevoflurane induces neurobehavioral and neuroendocrine abnormalities in exposed male rats (generation F0) and neurobehavioral, but not neuroendocrine, abnormalities in their male, but not female, offspring (generation F1). These effects of sevoflurane are accompanied by a hypermethylated neuron-specific K-2Cl (Kcc2) Cl exporter gene in the F0 spermatozoa and the F1 male hypothalamus, while the gene's expression is reduced in the F0 and F1 hypothalamus. We investigated whether inhibition of deoxyribonucleic acid methyltransferases (DNMTs) before paternal sevoflurane exposure could alleviate the anesthetic's F0 and F1 effects. METHODS: Sprague-Dawley male rats were anesthetized with 2.1% sevoflurane for 5 hours on postnatal day (P) 5 and mated with control females on P90 to generate offspring. The nonselective DNMT inhibitor decitabine (0.5 mg/kg, intraperitoneally) was administered 30 minutes before sevoflurane exposure. The F0 and F1 male rats were evaluated in in vivo and in vitro tests in adulthood. RESULTS: Paternal exposure to sevoflurane induced impaired prepulse inhibition of the acoustic startle response and exacerbated corticosterone responses to stress in F0 males and impaired prepulse inhibition of the startle responses in F1 males. These effects were accompanied in both generations by reduced and increased expressions of hypothalamic Kcc2 and Dnmt3a/b, respectively. Decitabine deterred the effects of paternal exposure to sevoflurane in F0 and F1 males. CONCLUSIONS: These results suggest that similar decitabine-sensitive mechanisms regulating expression of multiple genes are involved in the mediation of neurobehavioral abnormalities in sires neonatally exposed to sevoflurane and in their future unexposed male offspring.


Assuntos
Anestesia por Inalação/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Decitabina/uso terapêutico , Exposição Paterna/efeitos adversos , Sevoflurano/efeitos adversos , Animais , Animais Recém-Nascidos , Corticosterona/metabolismo , Metilases de Modificação do DNA/antagonistas & inibidores , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Reflexo de Sobressalto/efeitos dos fármacos , Estresse Psicológico/metabolismo , Simportadores/antagonistas & inibidores
10.
PLoS One ; 15(8): e0237377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785263

RESUMO

BACKGROUND: It is known that bioenergetics of aerobic and resistance exercise are not the same but both can effectively improve depression. However, it is not clear whether and how different types of exercise can influence depression through the same metabolic regulatory system. Metabolomics provides a way to study the correlation between metabolites and changes in exercise and/or diseases through the quantitative analysis of all metabolites in the organism. The objective of this study was to investigate the effects of aerobic and resistance training on urinary metabolites by metabolomics analysis in a rodent model of depression. METHODS: Male Sprague-Dawley rats were given chronic unpredictable mild stress (CUMS) for eight weeks. The validity of the modeling was assessed by behavioral indices. After four weeks of CUMS, the rats that developed depression were randomly divided into a depression control group, an aerobic training group and a resistance training group. There was also a normal control group. From week 5, the rats in the exercise groups were trained for 30 min per day, five days per week, for four weeks. The urine samples were collected pre and post the training program, and analyzed by proton nuclear magnetic resonance (1H-NMR) spectroscopy. RESULTS: Both types of training improved depression-like behavior in CUMS rats. Compared with normal control, 21 potential biomarkers were identified in the urine of CUMS rats, mainly involved in energy, amino acids and intestinal microbial metabolic pathways. Common responses to the training were found in the two exercise groups that the levels of glutamine, acetone and creatine were significantly recalled (all P<0.05) Aerobic training also resulted in changes in pyruvate and trigonelline, while resistance training modified α-Oxoglutarate, citric acid, and trimethylamine oxide (all P<0.05). CONCLUSIONS: Aerobic and resistance training resulted in common effects on the metabolic pathways of alanine-aspartate-glutamate, TCA cycle, and butyric acid. Aerobic training also had effects on glycolysis or gluconeogenesis and pyruvate metabolism, while resistance training had additional effect on intestinal microbial metabolism.


Assuntos
Metabolômica , Estresse Psicológico/metabolismo , Estresse Psicológico/urina , Aerobiose , Animais , Doença Crônica/psicologia , Metabolismo Energético , Masculino , Ratos , Ratos Sprague-Dawley , Treinamento de Resistência , Estresse Psicológico/fisiopatologia
11.
Gene ; 763: 145071, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-32827682

RESUMO

The previous study indicated that transport stress resulted in oxidative damage and autophagy/mitophagy elevation, companied by NOX1 over- expression in the jejunal tissues of pigs. However, the transportation-related gene expression profile and NOX1 function in intestine remain to be explicated. In the current study, differentially expressed genes involved in PI3K-Akt and NF-κB pathways, oxidative stress and autophagy process have been identified in pig jejunal tissues after transcriptome analysis following transportation. The physiological functions of NOX1 down-regulation were explored against oxidative damage and excessive autophagy in porcine intestinal epithelial cells (IPEC-1) following NOX1 inhibitor ML171 and H2O2 treatments. NOX1 down-regulation could decrease the content of Malondialdehyde (MDA), Lactic dehydrogenase (LDH) activity and reactive oxygen species (ROS) level, and up-regulate superoxide dismutase (SOD) activity. Furthermore, mitochondrial membrane potential and content were restored, and the expressions of tight junction proteins (Claudin-1 and ZO-1) were also increased. Additionally, NOX1 inhibitior could down-regulate the expression of autophagy-associated proteins (ATG5, LC3, p62), accompanied by activating SIRT1/PGC-1α pathway. NOX1 down-regulation might alleviate oxidative stress-induced mitochondria damage and intestinal mucosal injury via modulating excessive autophagy and SIRT1/PGC-1α signaling pathway. The data will shed light on the molecular mechanism of NOX1 on intestine oxidative damage following pig transportation.


Assuntos
Autofagia , Enterócitos/metabolismo , NADPH Oxidase 1/metabolismo , Estresse Oxidativo , Estresse Psicológico/metabolismo , Transcriptoma , Animais , Linhagem Celular , Feminino , Masculino , Mitocôndrias/metabolismo , NADPH Oxidase 1/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo , Estresse Psicológico/genética , Suínos
12.
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
13.
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
14.
Arterioscler Thromb Vasc Biol ; 40(8): 1830-1837, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32522007

RESUMO

OBJECTIVE: Adrenal gland secretes stress-induced glucocorticoids (iGCs) to coping with stress. Previous study showed that SR-BI (scavenger receptor BI) null (SR-BI-/-) mice failed to generate iGC in stress conditions, suggesting that SR-BI-mediated cholesterol uptake from HDL (high-density lipoprotein) is a key regulator for iGC production. However, the LDL (low-density lipoprotein)/LDLr (LDL receptor) pathway can also provide cholesterol for iGC synthesis, but rodents have limited LDL levels in circulation. Here, we generated SR-BI-/-ApoBtg (apolipoprotein B transgenic) mice with normal LDL levels in circulation to determine the relative contribution of the HDL/SR-BI and LDL/LDLr pathways to iGC production in stress conditions. Approach and Results: To obtain mouse models with normal LDL levels, SR-BI-/- mice were bred to ApoBtg mice. Then, the F1 SR-BI±ApoBtg mice were backcrossed to SR-BI-/- to obtain SR-BI-/-ApoBtg, SR-BI-/-ApoBwt (apolipoprotein B wild type), and SR-BI+/+ApoBtg mice. We first examined the lipoprotein profile, which shows a 6.5-fold increase in LDL levels in SR-BI-/-ApoBtg mice compared with SR-BI-/-ApoBwt mice. Then, we induced stress with adrenocorticotropic hormone and cecal ligation and puncture. One hour after adrenocorticotropic hormone stimulation, SR-BI+/+ApoBtg control mice produced iGC (14.9-fold), but both SR-BI-/-ApoBwt and SR-BI-/-ApoBtg showed no iGC production (P<0.001). Three hours after cecal ligation and puncture treatment, SR-BI+/+ApoBtg control mice showed iGC production (6.4-fold), but both SR-BI-/-ApoBwt and SR-BI-/-ApoBtg mice showed no iGC production (P<0.001). CONCLUSIONS: SR-BI-/-ApoBtg mice fail to produce iGC in stress conditions even though with restored LDL levels in circulation. These findings clarify that the HDL/SR-BI, not LDL/LDLr, pathway is responsible for iGC production in stress conditions.


Assuntos
Glucocorticoides/biossíntese , Receptores de LDL/fisiologia , Receptores Depuradores Classe B/fisiologia , Estresse Psicológico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Animais , Lipoproteínas LDL/sangue , Camundongos , Camundongos Endogâmicos C57BL
15.
PLoS One ; 15(6): e0233979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492052

RESUMO

BACKGROUND: Exposure to maternal stress during pregnancy can have adverse effects on the fetus, which has potential long-term effects on offspring´s development and health. We investigated the kinetics and metabolism of the hormones and amino acids: cortisol, cortisone, tryptophan and serotonin in the term placenta in an ex vivo human placental perfusion model. The placentas used in the experiments were donated from families participating in the Maternal Stress and Placental Function project with a known maternal stress background. METHOD: Cortisol, cortisone, tryptophan and serotonin were added simultaneously to the maternal side in the 6 hour ex vivo term human recirculating placental perfusion model, in four experimental set-ups: without inhibitors, with carbenoxolone -that inhibits cortisol metabolism into cortisone, with fluoxetine that inhibits the serotonin transporter, and with PCPA that inhibits metabolism of tryptophan into serotonin. The concentration of cortisol and cortisone, and tryptophan and serotonin were quantified using UPLC and HPLC-MS respectively. RESULTS: Cortisol was rapidly metabolized into cortisone in the placenta, to a somewhat lesser degree when adding the inhibitor carbenoxolone, resulting in higher fetal exposure to cortisol. Serotonin was also rapidly metabolized in the placenta. When adding fluoxetine a peak of fetal serotonin levels was seen in the first hour of the perfusion. No effect was seen of the maternal stress levels on placental transport kinetics in this study. CONCLUSION: Inhibiting the metabolism of cortisol in the placenta increased fetal exposure to cortisol as expected. Unexpectedly we saw an increased fetal exposure to serotonin when inhibiting the serotonin transporter, which may be related to the increased serotonin concentration on the maternal side of the placenta. No effect on placental kinetics were evident on maternal stress levels during the pregnancy as the majority of participating mothers had normal stress levels.


Assuntos
Feto/metabolismo , Troca Materno-Fetal , Placenta/metabolismo , Estresse Psicológico/metabolismo , Adulto , Cortisona/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Perfusão , Gravidez , Serotonina/metabolismo , Triptofano/metabolismo
16.
Psychopharmacology (Berl) ; 237(8): 2305-2316, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32506233

RESUMO

RATIONAL: The ability of conditioned stimuli to affect instrumental responding is a robust finding from animal as well as human research and is assumed as a key factor regarding the development and maintenance of addictive behaviour. OBJECTIVES: While it is well known that stress is an important factor for relapse after treatment, little is known about the impact of stress on conditioned substance-associated stimuli and their influence on instrumental responding. METHODS: We administered in the present study a Pavlovian-to-instrumental transfer (PIT) paradigm with stimuli associated with smoking- and chocolate-related rewards using points in a token economy to light to moderate smokers who also indicated to like eating chocolate. After completion of the first two phases of the PIT paradigm (i.e. Pavlovian training and instrumental trainings), participants were randomly allocated to the socially evaluated cold pressor test or a control condition before the final phase of the PIT paradigm, the transfer phase, was administered. RESULTS: The presentation of a smoking-related stimulus enhanced instrumental responding for a smoking-related reward (i.e. 'smoking-PIT' effect) and presentation of a chocolate-related stimulus for a chocolate-related reward (i.e. 'chocolate-PIT' effect) in participants aware of the experimental contingencies as indicated by expectancy ratings. However, acute stress did not change (i.e. neither enhanced nor attenuated) the 'smoking-PIT' effect or the 'chocolate-PIT' effect, and no overall effect of acute stress on tobacco choice was observed in aware participants. CONCLUSIONS: The established role of stress in addiction appears not to be driven by an augmenting effect on the ability of drug stimuli to promote drug-seeking.


Assuntos
Condicionamento Clássico/fisiologia , Recompensa , Estresse Psicológico/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transferência de Experiência/fisiologia , Doença Aguda , Adolescente , Adulto , Animais , Comportamento Aditivo/metabolismo , Comportamento Aditivo/psicologia , Temperatura Baixa/efeitos adversos , Feminino , Humanos , Hidrocortisona/análise , Hidrocortisona/metabolismo , Masculino , Distribuição Aleatória , Estresse Psicológico/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Adulto Jovem
17.
Sci Rep ; 10(1): 7236, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350298

RESUMO

Emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling with studies on stress-induced endocannabinoid dysregulation focusing on cerebral changes that are temporally proximal to stressors. Little is known about temporally distal and sex-specific effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Following limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids, related lipids, and mRNA were assessed, and behavioral performance evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar interpositus nucleus in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Cerebellar interpositus transcriptomics revealed substantial sex effects, with minimal stress effects. Stress did impair novel object recognition in both sexes and social preference in females. Accordingly, the cerebellar endocannabinoid system exhibits robust sex-specific differences, malleable through early-life stress, suggesting the role of endocannabinoids and stress to sexual differentiation of the brain and cerebellar-related dysfunctions.


Assuntos
Endocanabinoides/metabolismo , Hipocampo , Caracteres Sexuais , Maturidade Sexual , Estresse Psicológico , Animais , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Ratos , Ratos Long-Evans , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia , Estresse Psicológico/fisiopatologia
18.
Nature ; 581(7807): 204-208, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32405000

RESUMO

It has been speculated that brain activities might directly control adaptive immune responses in lymphoid organs, although there is little evidence for this. Here we show that splenic denervation in mice specifically compromises the formation of plasma cells during a T cell-dependent but not T cell-independent immune response. Splenic nerve activity enhances plasma cell production in a manner that requires B-cell responsiveness to acetylcholine mediated by the α9 nicotinic receptor, and T cells that express choline acetyl transferase1,2 probably act as a relay between the noradrenergic nerve and acetylcholine-responding B cells. We show that neurons in the central nucleus of the amygdala (CeA) and the paraventricular nucleus (PVN) that express corticotropin-releasing hormone (CRH) are connected to the splenic nerve; ablation or pharmacogenetic inhibition of these neurons reduces plasma cell formation, whereas pharmacogenetic activation of these neurons increases plasma cell abundance after immunization. In a newly developed behaviour regimen, mice are made to stand on an elevated platform, leading to activation of CeA and PVN CRH neurons and increased plasma cell formation. In immunized mice, the elevated platform regimen induces an increase in antigen-specific IgG antibodies in a manner that depends on CRH neurons in the CeA and PVN, an intact splenic nerve, and B cell expression of the α9 acetylcholine receptor. By identifying a specific brain-spleen neural connection that autonomically enhances humoral responses and demonstrating immune stimulation by a bodily behaviour, our study reveals brain control of adaptive immunity and suggests the possibility to enhance immunocompetency by behavioural intervention.


Assuntos
Comportamento Animal/fisiologia , Encéfalo/fisiologia , Imunidade Humoral/imunologia , Baço/imunologia , Baço/inervação , Acetilcolina/metabolismo , Acetilcolina/farmacologia , Neurônios Adrenérgicos/metabolismo , Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Colina O-Acetiltransferase/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Hemocianinas/imunologia , Imunoglobulina G/imunologia , Ativação Linfocitária , Masculino , Camundongos , Núcleo Hipotalâmico Paraventricular/citologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Plasmócitos/citologia , Plasmócitos/efeitos dos fármacos , Plasmócitos/imunologia , Receptores Nicotínicos/deficiência , Receptores Nicotínicos/metabolismo , Baço/citologia , Baço/efeitos dos fármacos , Estresse Psicológico/imunologia , Estresse Psicológico/metabolismo , Linfócitos T/imunologia
19.
Life Sci ; 254: 117790, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32416165

RESUMO

AIMS: To examine the differences in the hippocampal proteome profiles of resilience or susceptibility to chronic social isolation (CSIS), animal model of depression, and to identify biomarkers that can distinguish the two. MAIN METHODS: Comparative subproteomic approach was used to identify changes in hippocampal cytosol and nonsynaptic mitochondria (NSM) of CSIS-resilient compared to CSIS-sensitive or control rats. The resilient and sensitive phenotypes of CSIS rats were distinguished based on their sucrose preference values. Selected proteins were validated by Western blot or immunofluorescence. KEY FINDINGS: Predominantly down-regulated processes such as cytosolic cytoskeleton organization, the calcium signaling pathway, ubiquitin proteasome degradation, redox system, malate/aspartate shuttling and glutamate metabolism in CSIS-resilient compared to CSIS-sensitive rats were found. Decreased protein expression of glycolytic enzymes with simultaneous increased expression of Aco2 involved in tricarboxylic acid cycle and expression of several subunits composing oxidative phosphorylation involved enzymes (Uqcrc2, Atp5f1a, Atp5f1b) were found, indicating shift in energy production from glycolysis to oxidative phosphorylation in NSM. The four-fold higher level of mitochondrial glyceraldehyde-3-phosphate dehydrogenase of resilient rats indicated its transfer from the cytosol to the NSM. An increased level of transketolase along with the reduced pyruvate kinase level suggested an activated pentose phosphate pathway in CSIS-resilient relative to control rats. Cytosolic up-regulated CSIS proteins were implicated in antioxidative and proteasomal systems, while down-regulated NSM protein was involved in oxidative phosphorylation. SIGNIFICANCE: The identified altered activated pathways and potential biomarkers enhance understanding of molecular mechanisms underlying resilience or susceptibility to CSIS, crucial in developing new therapeutic strategies.


Assuntos
Glicólise , Hipocampo/metabolismo , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Proteômica , Resiliência Psicológica , Estresse Psicológico/metabolismo , Animais , Biomarcadores/metabolismo , Masculino , Fenótipo , Ratos , Isolamento Social
20.
PLoS One ; 15(4): e0227721, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298298

RESUMO

Speech fluency can be impaired in stressful situations. In this study, it was investigated whether a verbal fluency task by itself, i.e. without the presence of any further stressors, induces responses of the hypothalamic-pituitary adrenal (HPA) axis and of the sympathetic nervous system (SNS). The sample consisted of n = 85 participants (68.2% female; 33.3 ± 15.2 years) who performed two consecutive verbal fluency tasks for two minutes each. The categories were either 'stress' or 'disease' and 'animals' or 'foods' which were presented in a randomized order. Three saliva samples were collected, prior to the task (t0), immediately after (t1), and ten minutes after it (t2). Salivary α-amylase and cortisol were assessed. Furthermore, blood pressure, heart rate, and ratings of actual stress perception, level of effort, and tiredness were measured. The verbal fluency task induced a HPA axis response with a maximum cortisol level at t2 which was independent of task performance. Furthermore, perceived stress and effort, as well as tiredness increased after the task. Moreover, tiredness immediately after the task was negatively correlated with task performance. No α-amylase, blood pressure, or heart rate, and therefore SNS, responses were found. Implications for the integrated specificity model are discussed. We conclude that a verbal fluency task acts like an acute stressor that induces a cortisol and a perceived stress response without the need for further (e.g., social-evaluative) stress components. Therefore, it is a less time-consuming alternative to other stress tasks that can be used in field studies with little effort.


Assuntos
Cognição/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Fala/fisiologia , Estresse Psicológico/metabolismo , Adolescente , Adulto , Idoso , Feminino , Voluntários Saudáveis , Humanos , Hidrocortisona/análise , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Saliva/química , alfa-Amilases Salivares/análise , alfa-Amilases Salivares/metabolismo , Estresse Psicológico/fisiopatologia , Sistema Nervoso Simpático/fisiologia , Adulto Jovem
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