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Background: Persistent stress contributes to the onset and maintenance of problem gambling (PG), increasing risks for physiological disturbances. However, minimal research examines acute stress effects and relationships with PG features such as impulsivity or gambling urges. Purpose: The current study examines multiple facets of acute subjective and physiological stress responses in PG. Stress effects on gambling urges and relationships with impulsivity are also explored. Methods: A PG (n=21) and healthy control (HC; n=21) group were exposed to acute psychosocial stress. Saliva samples were collected while participants completed self-report measures of mood and gambling urges. Gambling urges, salivary cortisol (sC), salivary alpha-amylase (sAA), and subjective stress reactivity and recovery were compared within and between groups from baseline up to an hour following stress. Relationships between trait impulsivity, gambling urges, and all aspects of the acute stress response were examined. Results: The PG group showed blunted sC reactivity but reported heightened mood disturbances compared to HCs, while sAA levels did not differ between groups. Within PG and HC groups, sAA had a more rapid acute stress onset than sC, but between-marker differences were pronounced in PG. Self-reported gambling urges were high among PG participants but remained relatively unchanged following acute stress. Impulsivity was positively associated with gambling urges, however, it was not correlated with the acute stress response. Conclusions: This study provides a novel and wide-ranging assessment of the acute stress response in PG, for which research is currently limited. These results indicate that high stress in PG contributes to multi-faceted alterations of the acute stress response relative to HCs. Self-reported gambling urges are elevated and associated with greater trait impulsivity in PG but are unaffected by acute stress exposure. Our findings provide insight into acute stress processing dysfunction in PG and have implications for potential harms, such as increased suicide risk. / Thesis / Master of Science (MSc) / Chronic or continuous life stress can increase the risk of developing and sustaining gambling problems. The current study assessed the effects of a 20-minute stressful task on mood, physiological reactions, the desire to gamble, and their relationships with impulsivity in healthy individuals compared to those with problem gambling (PG). Results showed that after the stressor, the PG group reported more negative mood, but physiological reactions were reduced when compared to healthy participants. In individuals with PG, a greater desire to gamble was correlated with being more impulsive. Overall, our findings show that the long-term stress typically experienced by individuals with PG can affect their mental and physiological reactions to temporary stressors. Additionally, more impulsive individuals show a greater desire to gamble, which may contribute to problematic gambling behaviours. Future research should assess the life impacts of chronic stress in PG, such as the risk of gambling relapse and suicide.

L’équilibre alimentaire entre les AGPI n-6 et les AGPI n-3 joue probablement un rôle important dans le fonctionnement du système nerveux central et notamment dans la régulation de la neurotransmission. Des études suggèrent qu’une déficience en AGPI n-3 renforcerait la sensibilité des individus à des agressions de type chronique, tel que le stress ou le vieillissement. Notre objectif était de caractériser l’impact des apports alimentaires en AGPI n-3 sur la réponse à un stress chronique. Pour cela, la régulation de paramètres biochimiques, comportementaux et électrophysiologiques par un stress chronique de contention a été évaluée chez le rat recevant différents apports alimentaires en AGPI n-3 (déficients en AGPI n-3 ; équilibrés ; enrichis en AGPI-LC n-3). L’influence des glucocorticoïdes (hormones impliquées dans la réponse au stress) et des AGPI sur des fonctions cellulaires participant à la transmission synaptique a été analysée in vitro par des mesures de libération de neurotransmetteurs sur la lignée neuroblastique SH_SY5Y et par l’analyse des propriétés régulatrices astrocytaires en culture primaire.Nos résultats montrent que, chez le rat, la réponse au stress est modulée par les apports alimentaires en AGPI n-3 : la déficience en AGPI n-3 accentue la sensibilité au stress, notamment la réduction de l’activité locomotrice et la sensibilité aux environnements anxiogènes ; à l’inverse, l’enrichissement en AGPI-LC n-3 atténue la réponse au stress chronique, en réduisant la perte de poids, le pic de corticostérone plasmatique et la réponse émotionnelle. Comme le suggèrent les résultats obtenus in vitro, ces effets sont liés à des régulations complexes par les AGPI et les glucocorticoïdes des paramètres de libération de neurotransmetteur, de la plasticité morphologique astrocytaire et de la capacité de capture du glutamate par les astrocytes. / Dietary balance between n-6 PUFA and n-3 PUFA probably plays a major role in the regulation of brain function. Some studies suggest that an n-3 PUFA deficiency exacerbates the sensitivity of individuals to emotional disturbances, such as chronic stress. The aim of our work was to determine the impact of n-3 PUFA dietary intakes on stress response. The regulation of biochemical, electrophysiological and behavioural parameters by chronic restraint stress has been evaluated in rats receiving different n-3 PUFA supplies (n-3 PUFA deficient, balanced, n-3 LC-PUFA enriched). In parallel, we have conduced an in vitro study to characterize the effects of glucocorticoids (one of the major hormone involved in stress response) and of PUFA on the release of neurotransmitter (in human neuroblastoma SH_SY5Y cells) and on several astrocytic properties involved in synaptic regulation (in primary culture of rat astrocytes). In rats, we have shown that stress response is modulated by the n-3 PUFA status: the n-3 PUFA deficiency exacerbated the sensibility to stress, by aggravating the reduction of locomotor activity and the sensibility to anxiogenic environment; conversely, the n-3 LC-PUFA enrichment reduced rat responses to chronic stress, by limiting the weight loss, the increase in plasma corticosterone and the emotional response. As suggested by the results obtained in vitro, these effects are linked to complex influences of PUFA and glucocorticoids on the release of neurotransmitter and on astroglial morphological plasticity and glutamate uptake capacity.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-12T18:00:24Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) CARLOS BORGES FILHO.pdf: 1634053 bytes, checksum: f644f69e5e2309834c31b95712982bd3 (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-12T18:00:55Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) CARLOS BORGES FILHO.pdf: 1634053 bytes, checksum: f644f69e5e2309834c31b95712982bd3 (MD5) / Made available in DSpace on 2017-06-12T18:00:55Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) CARLOS BORGES FILHO.pdf: 1634053 bytes, checksum: f644f69e5e2309834c31b95712982bd3 (MD5) Previous issue date: 2016-12-30 / A depressao e uma doenca altamente incapacitante e que tem acometido um percentual crescente da populacao mundial. Ainda que varios antidepressivos estejam comercialmente disponiveis ha decadas, os efeitos colaterais destas drogas, aliados ao fato de que nem todos os pacientes respondem satisfatoriamente ao tratamento, levam a uma busca continua por novas alternativas para o tratamento ou complementacao do tratamento da depressao. Assim, expande-se cada vez mais o numero de estudos que avaliam compostos candidatos a antidepressivos. Neste contexto e que o efeito tipo-antidepressivo da crisina, um flavonoide natural abundante no maracuja do mato (Passiflora coerulea), em camundongos submetidos ao estresse cronico imprevisivel (UCS) foi demonstrado anteriormente por nosso grupo. No entanto, os fatores neuroquimicos associados a este efeito carecem de maiores investigacoes. Deste modo, o objetivo deste estudo foi avaliar os fatores neuroquimicos associados ao efeito tipo-antidepressivo do flavonoide crisina em dois modelos animais de depressao, o modelo do UCS e o modelo da bulbectomia olfatoria (OB), ambos em camundongos. No modelo do UCS foram avaliados o cortex pre-frontal (PFC) e o hipocampo (HP), enquanto no modelo da OB foi avaliado o HP. O UCS e a OB induziram um comportamento tipo-depressivo, caracterizado pela diminuicao no tempo de lambida no teste de borrifagem de sacarose e pelo aumento no tempo de imobilidade no teste de suspensao de cauda ou no teste de nado forcado. Ainda, a OB ocasionou alteracoes no teste de campo aberto, decorrentes da hiperatividade caracteristicamente induzida por este modelo. O tratamento oral com crisina (5 ou 20 mg/kg, durante 28 dias no modelo do UCS, e por 14 dias no modelo da OB), de forma semelhante a fluoxetina (10 mg/kg, controle positivo), culminou na prevencao destas alteracoes, confirmando a acao tipo-antidepressiva da crisina nos parametros comportamentais avaliados. O UCS ocasionou o aumento nos niveis plasmaticos do hormonio liberador de corticotrofina, do hormonio adrenocorticotrofico, e a atividade das caspases 3 e 9 nas estruturas cerebrais avaliadas, enquanto a OB ocasionou a reducao dos niveis hipocampais do fator neurotrofico derivado do encefalo. O UCS e a OB resultaram no aumento dos niveis de citocinas proinflamatorias nas estruturas cerebrais avaliadas, como fator de necrose tumoral-α, interferon- γ, interleucina-1β, interleucina-6, alem do aumento dos niveis de quinurenina. O UCS e a OB tambem induziram a diminuicao dos niveis de 5-hidroxitriptamina (5-HT) e o aumento da 11 atividade da enzima indoleamina-2,3-dioxigenase. O tratamento com crisina, de forma semelhante a fluoxetina, promoveu a atenuacao de todas estas alteracoes ocasionadas pelo UCS ou pela OB. Em suma, os resultados deste estudo vem a corroborar com a hipotese de que o flavonoide crisina e um alvo potencial no estudo de novas alternativas para o tratamento ou para a complementacao do tratamento da depressao. Adicionalmente, este trabalho indica a associacao das citocinas pro-inflamatorias, da via da quinurenina, do metabolismo da 5-HT, das neurotrofinas e da atividade das caspases na acao tipo-antidepressiva exercida pela crisina em camundongos expostos ao UCS ou a OB. Finalmente, o presente trabalho expoe o maracuja do mato como um importante alvo para o estudo dos produtos naturais no combate a depressao, mostrando a fundamentalidade da investigacao da funcionalidade e constituicao bioativa desta e outras plantas do bioma pampa. / Depression is a highly incapacitating disease that has affected a crescent percentage of the world population. Although various antidepressants have been commercially available for decades, the side effects of these drugs, together with the fact that not all patients respond satisfactorily to treatment, lead to continuous search for new alternatives for the treatment or supplementary treatment of depression. Thus, the number of studies evaluating compounds candidate to antidepressants expands increasingly. In this context, the antidepressant-like effect of chrysin, a natural flavonoid abundant in passion fruit bush (Passiflora coerulea), in mice subjected to unpredictable chronic stress (UCS) has been previously demonstrated by our group. However, neurochemical factors associated with this effect require further investigations. Thus, the objective of this study was to evaluate the neurochemical factors associated with the antidepressant-like effect of chrysin in two animal models of depression, the model of UCS and the model of olfactory bulbectomy (OB), both in mice. In the UCS model the prefrontal cortex (PFC) and the hippocampus (HP) were evaluated, in the OB model the HP was evaluated. The UCS and OB induced a depressive-like behavior, characterized by the decrease in the total time of grooming in the splash test and by increase on immobility time in the tail suspension test or forced swimming test. Still, OB induced changes in open field test, resulting from the hyperactivity characteristically induced by this model. The oral treatment with chrysin (5 or 20 mg/kg for 28 days in the UCS model and for 14 days in OB model), similarly to fluoxetine (10 mg/kg, positive control) resulted in the prevention of these changes, confirming the antidepressant-like action of chrysin in the behavioral parameters evaluated. The UCS led to an increase in plasma levels of corticotropin-releasing hormone, adrenocorticotropic hormone and activity of caspases 3 and 9 in the brain structures evaluated, while the OB caused a reduction of hippocampal levels of brain-derived neurotrophic factor. The UCS and OB resulted in increase of proinflammatory cytokines levels in the brain structures evaluated, such as tumor necrosis factor-α, interferon- γ, interleukin-1β, interleukin-6, and increase kynurenine levels. UCS and OB also induced the decrease in 5-hydroxytryptamine (5-HT) levels and the increase of the activity of indoleamine-2,3-dioxygenase enzyme. Treatment with chrysin, similarly to fluoxetine, 13 promoted the attenuation of all these changes caused by UCS or OB. In summary, results of this study come to corroborate the hyphotesis that the flavonoid chrysin is a potential target in the study of new alternatives for the treatment or complement treatment of depression. Additionally, this study indicates the association of pro-inflammatory cytokines, of kynurenine pathway, of 5-HT metabolism, of neurotrophins and of caspases activities in the antidepressant-like action exerted by chrysin in mice exposed to UCS or OB. Finally, this paper exposes the passion bush as an important target for the study of natural products to combat depression, showing the importance of research of functionality and bioactive constitution of this and other plants of the pampa biome.

Submitted by (edna.saturno@ufrpe.br) on 2017-02-22T16:32:41Z No. of bitstreams: 1 Victor Andrade da Silva.pdf: 390078 bytes, checksum: c2381631004f76239866e7fbd989d9a9 (MD5) / Made available in DSpace on 2017-02-22T16:32:41Z (GMT). No. of bitstreams: 1 Victor Andrade da Silva.pdf: 390078 bytes, checksum: c2381631004f76239866e7fbd989d9a9 (MD5) Previous issue date: 2013-02-27 / Stocking density is recognized as a critical factor in aquaculture, since high densities represent a potential source of chronic stress. This study investigated the effects of a chronic stressor, such as high stocking densities, on growth, physiological responses, and flesh quality of juvenile cobia (Rachycentron canadum) tested for a period of 42 days. The trial was conducted in a recirculating aquaculture system equipped with tanks of 70 L tanks. Cobia of 46.32 ± 0.22 g (mean ± SEM) were randomly distributed into three stocking densities (3.30 ± 0.02; 6.67 ± 0.03; 13.15 ± 0.16 g L-1), and three replicates. Treatment groups were nominally assigned as low density (LD; 5 fish/tank), medium density (MD; 10 fish/tank), and high density (HD; 20 fish/tank), respectively. Plasma concentrations of cortisol, osmolality and lactate were not affected by density levels, and values were according with those reported as basal for juvenile cobia. However, growth rate were influenced by density levels, in which weight gain and specific growth rate were significantly higher in the LD group. Drip loss did not differ among density groups. However, stocking density influenced the onset and development of rigor mortis. Our findings indicated that rearing juvenile cobia at the high densities negatively affected growth rate and flesh quality. Results suggest that juvenile cobia reared at the high densities were able to counteract stress. However, energy from the diet and/or body reserves was diverted from growth as a response to the elevated metabolic demand caused by stress. In this regard, juvenile cobia should be maintained at a final biomass up to approximately 15 kg m-3 to ensure a maximal growth rate and an improved final product quality. To our knowledge, this is the first report assessing the influence of a chronic stressor on both physiological responses and flesh quality parameters in cobia. This may provide information to the advancement of cobia aquaculture, leading to improvements in fish welfare, final product quality and increased productivity. / A densidade de estocagem é amplamente reconhecida como um fator crítico em aquicultura, uma vez que altas densidades representam uma potencial fonte de estresse crônico. Este estudo avaliou a resposta fisiológica, desempenho zootécnico e qualidade de filé de juvenis de beijupirá (Rachycentron canadum) submetidos a um estressor crônico, como altas densidades, visando à definição de condições de criação que levem à melhoria do bem estar animal e ao incremento da produtividade e qualidade do produto final. Os peixes foram testados por um período de 42 dias, em que juvenis de 46,32 ± 0,22 g (média ± erro padrão) foram aleatoriamente distribuídos em três densidades (3,30 ± 0,02; 6,67 ± 0,03; 13,15 ± 0,16 g L-1), e em três repetições. Os tratamentos foram designados como baixa densidade (LD; 5 peixe/tanque), densidade média (MD; 10 peixe/tanque), e alta densidade (HD; 20 peixes/tanque), respectivamente. As concentrações de cortisol e lactato e a osmolalidade do plasma sanguíneo não foram afetadas pela densidade de estocagem, e seus valores estavam de acordo com as faixas basais previamente relatados para juvenis de beijupirá. No entanto, o ganho de peso e a taxa de crescimento específico foram significativamente maiores no grupo LD. A densidade de estocagem também influenciou o início e o desenvolvimento do rigor mortis. Juvenis de beijupirá criados na alta densidade apresentaram menor taxa de crescimento e qualidade de filé. Os resultados sugerem que juvenis de beijupirá criados nas altas densidades foram capazes de contrapor o estresse ao nível de composição do plasma. Contudo, energia da dieta e/ou reservas do corpo podem ter sido desviadas do crescimento como resposta à alta demanda metabólica causada pelo estresse. Dessa forma, o presente estudo sugere que juvenis de beijupirá devem ser mantidos em uma biomassa final de até 15 kg m-3, aproximadamente para garantir máximo crescimento e melhor qualidade do produto final. Aparentemente, este estudo é o primeiro a abordar a influencia de um estresse crônico na resposta fisiológica e qualidade de filé de juvenis de beijupirá. Os resultados podem fornecer informações para avanços na criação dessa espécie, conduzindo a melhorias no bem estar animal, na qualidade do produto final e no aumento da produtividade

Un tiers des patients déprimés inclus dans les essais cliniques ne répondent pas à un traitement antidépresseur. La dérégulation de l’axe HPA et la réduction de la neurogènese hippocampique sont les principaux facteurs de la résistance aux antidépresseurs. L’objectif de ce travail est de développer un modèle de résistance à l’antidépresseur lié à l’axe HPA et d’utiliser ce modèle pour comprendre les mécanismes sous-jacents. Nos résultats suggèrent qu'une mauvaise régulation de rétrocontrôle négatif de l'axe HPA au début du protocole peut être un facteur prédictif de l'échec du traitement antidépresseur dans la dépression. Notre protocole montre que l’échec de la fluoxétine à induire des effets antidépresseurs a été associé à une mauvaise aptitude des composés à stimuler la prolifération des cellules dans le gyrus denté de l'hippocampe. D'autres études sont nécessaires pour étudier la relation de causalité entre ces phénomènes. / One-third of depressed patients included in clinical trials do not respond to antidepressant treatment. Dysregulation of the HPA axis and reduced hippocampal neurogenesis are the main factors of resistance to antidepressants. The objective of this work is to develop a model of resistance to antidepressant related to the HPA axis and to use this model to understand the underlying mechanisms. Our results suggest that dysregulation of negative feedback of the HPA axis at the beginning of the protocol can be a predictor of antidepressant treatment failure in depression. Our protocol shows that the failure of fluoxetine to induce antidepressant effects was associated with poor ability of compounds to stimulate cell proliferation in the dentate gyrus of the hippocampus. Further studies are needed to investigate the causal relationship between these phenomena.

Current research in the field of emotions has demonstrated a strong causal correlation between stressful life events and clinical depression. The conceptual framework of this scientific study is taking into consideration the theoretical ideas developed by the laboratories of Alex Zautra, and Susan Folkman about the co-existence of positive and negative emotions during the experience of stress and depression. The principal purpose of this study is to report the convergent validity of the Multicultural State-Trait Depression Inventory, which supports the new direction in the psychometric assessment of clinical depression. Responses to the items of the state and trait scales were analyzed on a multicultural sample to determine the convergent validity and item analysis of the instrument. The results present empirical evidence that demonstrates a high degree of concurrent validity of the IMUDER subscalesand the reference instruments as shown by Pearson correlations. / Los estudios científicos de las emociones han demostrado concluyentemente una robusta relación causal entre eventos estresantes de la vida diaria y la depresión clínica. El marco conceptual del presente estudio toma en consideración los marcos teóricos de Alex Zautra y de Susan Folkman acerca de la coexistencia de emociones positivas y negativas en el proceso de estrés y depresión. El propósito de este estudio es reportar el análisis de ítems y la validez convergente del Inventario Multicultural de la Depresión, Estado-Rasgo (IMUDER). En base a una muestra multicultural, se realizó los análisis psicométricos en base al coeficiente de correlación de Pearson, a fin de determinar la validez convergente. Los resultados de dichos análisis realizados en forma separada para la escala estado y para la escala rasgo, nos indican un elevado nivel de asociación y validez convergente entre las escalas estado y rasgo del IMUDER, dimensiones de distres y eustres, y las pruebas de depresión utilizadas en este estudio. Estos datos indican que el IMUDER es un instrumento psicométrico que presentauna sólida validez convergente y propiedades psicométricas adecuadas.

Alterações nos ritmos circadianos estão envolvidas no desenvolvimento de transtornos metabólicos como obesidade e síndrome metabólica. Além disto, fatores ambientais como o consumo de alimentos altamente palatáveis ricos em gordura e a exposição a situações estressantes podem contribuir na incidência e severidade destas doenças crônicas. Neste estudo avaliamos os efeitos da associação de modelos animais de obesidade e estresse crônico sobre o padrão temporal dos níveis séricos de marcadores adipogênicos (adiponectina, leptina, triglicerídeos e colesterol total) e de corticosterona (para controle do modelo de estresse crônico) de ratos. Adicionalmente, para controle da eficácia do modelo de obesidade os seguintes parâmetros foram avaliados: ganho de peso (avaliação semanal); o delta de peso e o Índice de Lee e o peso de frações de tecido adiposo (mesentérico, MAT; subcutâneo, SAT; e pericárdico, PAT). Foram utilizados 98 ratos Wistar machos com 60 dias de idade tratados por 80 dias e divididos em 4 grupos: dieta padrão (C), dieta hipercalórica (dieta de cafeteria) (D), estresse crônico (estresse crônico por restrição 1h/dia/5 dias por semana, entre as 9h e as 12h) associado a dieta padrão (E), e estresse crônico associado a dieta hipercalórica (DE). Os animais foram mortos em 3 períodos do dia (7h -ZT0, 19h - ZT12 e 1h - ZT18). Nossos resultados comprovam que a exposição crônica a dieta hipercalórica é um modelo eficaz na indução de obesidade e de síndrome metabólica em ratos, aumentando o delta de peso, o índice de Lee, peso de frações de tecido adiposo, e os níveis de triglicerídeos e leptina. Adicionalmente confirmam a presença de um padrão temporal na liberação de triglicerídeos, corticosterona, adiponectina e leptina em animais controles. O estresse crônico reduziu o delta de peso, peso do tecido adiposo mesentérico e os níveis de triglicerídeos, colesterol total e de leptina. Houve interação entre estresse crônico e obesidade em colesterol total, e houve interação entre os pontos temporais e obesidade nos níveis de adiponectina e corticosterona, também houve interação entre os pontos temporais e estresse crônico nos níveis de leptina. Concluindo, ambos os parâmetros foram capazes de alterar o padrão temporal de triglicerídeos e leptina. Assim, o impacto da dessincronização de um organismo com fatores ambientais contribuem para o desenvolvimento de doenças metabólicas como obesidade e síndrome metabólica. / Changes in the circadian rhythms are involved in the development of metabolic disorders such as obesity and metabolic syndrome. Furthermore, environmental factors such as consumption of highly palatable food rich in fat and exposure to stressful situations may contribute to the incidence and severity of these diseases. In this study we evaluated the effects of the association animal models of obesity and chronic stress on the temporal pattern of serum levels of adipogenic markers (adiponectin, leptin, triglycerides and cholesterol), and of corticosterone (to control of chronic stress model) of rats. Additionally, to control the efficacy of obesity model the following parameters were evaluated: weight gain (weekly evaluation), the delta weight, the Lee index, and the weight fractions of adipose tissue (mesenteric, MAT; subcutaneous, SAT and pericardial, PAT). A total of 98 male Wistar rats at 60 days of age treated for 80 days and divided into 4 groups: standard diet (C), hypercaloric diet (cafeteria diet) (HD), chronic stress (chronic stress by restraint 1h/day/5 days a week between 9am and 12pm) associated with the standard diet (S), and chronic stress associated with hypercaloric diet (SHD). The animals were killed at 3 time points (7:00 a.m. -ZT0, 7:00 p.m. - ZT12 e 1:00 a.m. - ZT18). Our results show that chronic exposure to hypercaloric diet is an effective model to induce obesity and metabolic syndrome in rats, increasing the weight delta, Lee index, weight fractions of adipose tissue, triglycerides and leptin levels. Additionally, it was confirmed the presence of a temporal pattern in the release of triglycerides, corticosterone, adiponectin, leptin in naïve animals. The chronic stress reduced weight delta, the mesenteric adipose tissue weight and levels of triglycerides, cholesterol and leptin. There was interaction between chronic stress and obesity in the total cholesterol, and there was interaction between time points and obesity in adiponectin and corticosterone levels, also there was interaction between time points and chronic stress in leptin levels. In conclusion, both parameters were able of desynchronize the rhythms of leptin and triglycerides on temporal pattern. Thus, the impact of desynchronization of an organism with environmental factors contributes to the development of metabolic diseases such as obesity and metabolic syndrome.

Introdução: O ciclo sono-vigília, a alimentação e o metabolismo de lipídios e de glicose estão sujeitos à regulação circadiana a qual visa sincronizar a energia disponível e o gasto necessário para mudanças no meio externo de acordo com a fase claro-escuro. O desajuste do ritmo circadiano pode ser fator causal para uma relação positiva entre o trabalho noturno e obesidade. A exposição ao estresse crônico devido à liberação de glicocorticóides provoca distribuição anômala de gordura, principalmente em região abdominal que está associada à resistência a insulina, hipertrigliceridemia, e hipertensão arterial. A exposição ao estresse crônico é considerado um dessincronizador de ritmos biológicos, induz liberação de glicocorticoides esta associada a distúrbios alimentares que podem levar a obesidade. Objetivos: Este estudo objetiva avaliar o efeito da associação de modelos experimentais de estresse crônico e de obesidade sobre parâmetros bioquímicos, ponderais, nociceptivos e comportamentais. Adicionalmente, à avaliação do padrão temporal de glicose, insulina, grelina e corticosterona. Métodos: Foram utilizados 96 ratos Wistar machos com 60 dias de idade divididos em 4 grupos: dieta padrão (C), Dieta hipercalórica (dieta de cafeteria) (D), estresse crônico (estresse crônico por restrição 1h/dia/5 dias por semana, entre às 9h e às 12h) associado a dieta padrão (E), estresse crônico associado a dieta hipercalórica (DE). Após 80 dias de experimento os animais foram avaliados no campo aberto (atividade locomotora e exploratória), labirinto em cruz elevado (comportamento do tipo ansioso) e testes de formalina e tail-flick (comportamento da resposta nociceptiva). Após os animais foram mortos em 3 períodos do dia (7h -ZT0, 19h - ZT12 e 1h - ZT18) para avaliação dos níveis plasmáticos de glicose, insulina, corticosterona, e grelina. Resultados: Nossos resultados indicam que os animais que consumiram dieta hipercalórica apresentaram aumento na locomoção. Além disso, mostraram alterações comportamentais em relação ao comportamento do tipo ansioso em animais estressados. Adicionalmente, os ratos estressados que consumiram a dieta hipercalórica não diferiram do grupo controle em delta de peso, peso relativo das adrenais e nos níveis de corticosterona, indicando que o estabelecimento da obesidade é influenciado pela ativação crônica do eixo HHA indexada pela hipertrofia das adrenais observada no grupo de animais submetidos a estresse crônico. No entanto em animais estressados que consumiram a dieta hipercalórica não apresentaram hipertrofia das adrenais. Também confirmamos o padrão temporal dos hormônios corticosterona e insulina, porém, nos horários avaliados não foi possível detectar a existência do padrão temporal da grelina e da glicose. Adicionalmente, os níveis de corticosterona sofreram efeito do estresse crônico e interação entre obesidade e do horário do dia. Por outro lado, o padrão temporal da insulina sofreu efeito apenas da dieta. No entanto, os níveis glicêmicos sofreram os efeitos do consumo da dieta e interação entre dieta e estresse. Conclusão: Os resultados desta dissertação sugerem que a exposição ao estresse crônico e à obesidade influencia o padrão temporal de biomarcadores periféricos que podem ter impactos comportamentais e repercussões metabólicas. / Introduction: The sleep-wake cycle, feeding and metabolism of lipids and glucose are subject to circadian regulation, which aims to synchronize the available energy and expense required for changes in the external environment according to the light/dark phase. Such rhythms are coordinated by circadian clocks. Alterations in the circadian rhythm may be a causal factor for a positive relationship between shift work and obesity. Exposure of chronic stress due to release of glucocorticoids cause abnormal fat distribution, especially in the abdominal region that is associated with insulin resistance, hypertriglyceridemia, and hypertension. Exposure to chronic stress, which is related to biological rhythms desynchronized and induces release of glucocorticoids associated with eating disorders that can lead to obesity. Objectives: Since chronic stress is an important component of modern life often associated with binge eating and obesity this study aims to evaluate the effect of the combination of experimental models of chronic stress and obesity on weight, behavior and biochemical parameters, associated to evaluation of the temporal pattern of peripheral markers (glucose, insulin, ghrelin and corticosterone). Methods: Was used 96 male Wistar rats at 60 days old were divided into 4 groups: diet standard (C), hypercaloric diet (cafeteria diet) (HD), chronic stress (chronic stress by restricting 1h/day/5 days a week between 9am and 12pm for 80 days) associated with the standard diet (S), chronic stress associated with hypercaloric diet (SHD). After 80 days of experiment the animals were evaluated in the open field (locomotor and exploratory activities), elevated plus maze (anxiety-like behavior) and formalin tests and tail-flick (nociceptive response). After 24h the animals were killed in three periods of the day (ZT0-7h, ZT12-19h - and ZT18-1h) to evaluate plasma levels of glucose, insulin, corticosterone, and ghrelin. Results: Our results indicate that HD group increase in locomotion. Also, shows behavioral changes elevated plus maze test, such as anxiety. Additionally, SHD group did not differ from control group on delta weight, relative weight of the adrenals and corticosterone levels, indicating that the establishment of obesity is influenced by chronic HPA axis activation, which is indexed by adrenal hypertrophy observed in the group of animals subjected to chronic stress. However in stressed animals who consumed the high calorie diet showed no adrenal hypertrophy.We also demonstrated the temporal pattern of plasmatic levels corticosterone and insulin; however, it was not possible to detect the temporal pattern of ghrelin and glucose levels at the times analyzed. Additionally, corticosterone levels suffered effects of obesity, chronic stress and the time of day. Furthermore, the temporal pattern of insulin was affected only by obesity. However, glucose levels suffered the effects of obesity and interaction between obesity and chronic stress. Conclusion: The results of this work suggest that exposure to chronic stress and hypercaloric diet may influence the temporal pattern of peripheral biomarkers that which may impact on behavior and metabolism.

Submitted by Daniele Amaral (daniee_ni@hotmail.com) on 2016-10-05T20:44:37Z No. of bitstreams: 1 DissWCF.pdf: 1667974 bytes, checksum: eb02b0255d4c2035728b60b62b8627e0 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-20T16:21:42Z (GMT) No. of bitstreams: 1 DissWCF.pdf: 1667974 bytes, checksum: eb02b0255d4c2035728b60b62b8627e0 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-20T16:21:49Z (GMT) No. of bitstreams: 1 DissWCF.pdf: 1667974 bytes, checksum: eb02b0255d4c2035728b60b62b8627e0 (MD5) / Made available in DSpace on 2016-10-20T16:21:55Z (GMT). No. of bitstreams: 1 DissWCF.pdf: 1667974 bytes, checksum: eb02b0255d4c2035728b60b62b8627e0 (MD5) Previous issue date: 2016-03-31 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Emotional stress has been recognized as a risk factor for cardiovascular diseases. Nevertheless, the mechanisms involved in the etiology of cardiovascular dysfunctions evoked by stress are still poorly understood. Thus, in the present study we investigated the involvement of angiotensin II acting in the type 1 receptor (AT1) in cardiovascular dysfunctions evoked by chronic stress in rats. For this, we compared the effect of chronic treatment with the AT1 receptor antagonist losartana (30mg/kg/day, p.o.) in the cardiovascular and autonomic changes following 10 days exposure to chronic variable stress (CVS, heterotypic stressor) and repeated restraint stress (RRS, homotypic stressor). Neither RRS nor CVS affected basal values of arterial pressure and heart rate. However, RRS increased sympathetic tone to the heart and decreased cardiac parasympathetic activity, whereas CVS decreased cardiac parasympathetic activity. Both chronic stressors also impaired the baroreflex function. All alterations in autonomic activity and the baroreflex impairment were inhibited by treatment with losartan. Complementary measurements of parameters commonly analyzed in studies investigating stress effects also indicated that CVS reduced body weight gain and increased circulating corticosterone, but these effects were not affected by losartan. In fact, CVS-evoked body weight change was even higher in losartan-treated animals. In conclusion, these findings indicate an involvement of angiotensin II/AT1 receptors in autonomic changes evoked by both homotypic and heterotypic chronic stressors. Additionally, present results suggest that increased circulating corticosterone evoked by CVS is independent of AT1 receptors, while reduction in body weight gain evoked by this heterotypic stressor is facilitated by treatment with losartan. / Estresse emocional tem sido reconhecido como um fator de risco para o desenvolvimento de doenças cardiovasculares. No entanto, os mecanismos envolvidos na etiologia das disfunções cardiovasculares evocadas pelo estresse ainda são pouco compreendidos. Assim, no presente estudo nós investigamos o envolvimento da angiotensina II, agindo através do receptor tipo 1 (AT1), nas disfunções cardiovasculares evocadas por estresse crônico em ratos. Para isso, comparamos o efeito do tratamento crônico com um antagonista AT1, losartana (30 mg/kg/dia, p.o.), nas alterações cardiovasculares e autônomas após exposição por 10 dias a dois modelos de estresse crônico: o estresse crônico de variável (ECV, estressor heterotípico) e o estresse de restrição repetido (ERR, estressor homotípico). Nenhum dos protocolos de estresse crônico afetaram os valores basais de pressão arterial e frequência cardíaca. No entanto, o ERR aumentou o tônus simpático para o coração e diminuiu a atividade parassimpática cardíaca, enquanto o ECV diminuiu a atividade parassimpática cardíaca. Ambos os estressores crônicos também prejudicaram a função do barorreflexo. Todas as alterações na atividade autônoma e a disfunção do barorreflexo foram inibidas pelo tratamento com losartana. Medidas complementares de parâmetros comumente analisados em estudos investigando os efeitos do estresse também demonstraram que o nosso protocolo de ECV reduziu o ganho de peso e aumentou os níveis plasmáticos de corticosterona, porém nenhum destes efeitos foram afetados pelo tratamento com losartana. De fato, a redução no ganho de peso corporal induzida pelo ECV foi acentuada nos animais tratados com losartana. Em conclusão, estes resultados indicam um envolvimento dos receptores AT1 nas alterações autônomas evocadas pelos estressores homotípico e heterotípico. Além disso, os resultados do presente estudo sugerem que o aumento na corticosterona circulante causada pelo ECV é independente dos receptores AT1, enquanto a redução de ganho do peso corporal evocado por este estressor heterotípico é facilitado pelo tratamento com losartana.