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- ItemAcesso aberto (Open Access)Ação da Betametasona em Ratas Prenhes: Impacto sobre os Níveis de Corticosterona e Glândulas Adrenais Maternas e Fetais(Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2001-12-01) Souza, Eduardo de [UNIFESP]; Kobayashi, Sérgio; Simões, Manuel de Jesus [UNIFESP]; Camano, Luiz; Kulay Júnior, Luiz; Universidade Federal de São Paulo (UNIFESP)Purpose: the repetitive use of antenatal corticosteroid therapy for acceleration of fetal lung maturation has been common in cases at risk of preterm delivery. We studied the corticosterone levels at term and the morphologic aspects in the maternal and fetal adrenal glands submitted to the effect of betamethasone in the second half of rat pregnancy in order to verify its consequences. Methods: thirty female pregnant rats were divided into three groups of ten animals each. Group I received betamethasone on the 11th, 12th, 18th and 19th day of pregnancy. Group II received distilled water on the same days (control group). Group III did not receive any drug (stress control group). All rats were sacrificed on the 20th day of pregnancy when plasma corticosterone levels of dams were assessed and the maternal and fetal adrenal glands were studied by light microscopy. Results: plasma corticosterone level of dams was lower in the group treated with betamethasone (4.8 mg/dL) when compared with the control groups (17.7 and 26.8 mg/dL). The light microscopy study revealed cytoplasmatic vacuolation in the fasciculate zone in the maternal and fetal adrenal glands, which indicates adrenal suppression. Conclusions: the antenatal repetitive and prolonged use of corticosteroids in pregnant rats for acceleration of lung fetal maturation causes maternal and fetal adrenal suppression.
- ItemSomente MetadadadosAcute restraint differently alters defensive responses and fos immunoreactivity in the rat brain(Elsevier B.V., 2012-06-15) Andrade, José Simões de [UNIFESP]; Abrão, Renata Oliveira [UNIFESP]; Céspedes, Isabel Cristina [UNIFESP]; Garcia, Marcia Carvalho [UNIFESP]; Nascimento, Juliana Olivetti Guzman [UNIFESP]; Spadari-Bratfisch, Regina Celia [UNIFESP]; Melo-Thomas, Liana [UNIFESP]; Silva, Regina Cláudia Barbosa da [UNIFESP]; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Results from a previous study show that rats exposed to acute restraint display anxiogenic-like behavior, evidenced by facilitation of avoidance responses in the elevated T-maze (ETM) model of anxiety. in contrast, escape responses were unaltered by stress exposure. Since ETM avoidance and escape tasks seem to activate distinct sets of brain structures, it is possible that the differences observed with acute restraint are due to particularities in the neurobiological mechanisms which modulate these responses. in the present study, analysis of fos protein immunoreactivity (fos-ir) was used to map areas activated by exposure of male Wistar rats to restraint stress (30 min) previously (30 min) to the ETM. Corticosterone levels were also measured in stressed and non-stressed animals. Confirming previous observations restraint facilitated avoidance performance, an anxiogenic result, while leaving escape unaltered. Performance of the avoidance task increased fos-ir in the frontal cortex, intermediate lateral septum, basolateral amygdala, basomedial amygdala, lateral amygdala, anterior hypothalamus and dorsal raphe nucleus. in contrast, performance of escape increased fos-ir in the ventromedial hypothalamus, dorsolateral periaqueductal gray and locus ceruleus. Both behavioral tasks also increased fos-ir in the dorsomedial hypothalamus. Restraint significantly raised corticosterone levels. Additionally after restraint, fos-ir was predominantly seen in the basolateral amygdala and dorsal raphe of animals submitted to the avoidance task. This data confirms that different sets of brain structures are activated by ETM avoidance and escape tasks and suggests that acute restraint differently alters ETM behavior and the pattern of fos activation in the brain. (C) 2012 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosAdrenalectomy abolishes the food-induced hypothalamic serotonin release in both normal and monosodium glutamate-obese rats(Elsevier B.V., 2002-08-15) Guimaraes, Regina Barros [UNIFESP]; Telles, Monica Marques [UNIFESP]; Coelho, Vivian Beatriz Orlandin [UNIFESP]; Mori, Rosana Cristina Tieko [UNIFESP]; Nascimento, Claudia Maria da Penha Oller do [UNIFESP]; Ribeiro, Eliane Beraldi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Corticosteroids influence energy homeostasis through centrally-mediated stimulation of energy intake and inhibition of expenditure, while central serotonin (5-HT) has opposite effects. Both serotonergic dysfunction and high glucocorticoid levels may be relevant in obesity. the neurotoxin monosodium glutamate (MSG) induces a non-hyperphagic and hypometabolic obesity with hypercorticosteronemia. We investigated the influence of corticosterone levels on the serotonergic system of MSG-obese and control rats. Applying microdialysis, we found a similar feeding-induced stimulation of serotonin release in the lateral hypothalamus (LH) in sham-adrenalectomized control and MSG rats. the concomitant serum corticosterone variations were markedly distinct between them, in that an increase occurred in the control group, while the initially high levels of the MSG rats decreased with feeding. It is suggested that this lowering of corticosterone prevented a higher serotonergic activation, which would lead to a higher meal-induced thermogenesis and a better adequation of the,caloric intake to a low metabolism. Adrenalectomy completely abolished the feeding-evoked serotonergic stimulation in both groups. This observation demonstrates that glucocorticoids are necessary for food intake to acutely stimulate 5-HT release and indicates that serotonergic activity in the LH is not likely to participate in the adrenalectomy-induced attenuation of the MSG-obesity. (C) 2002 Elsevier Science Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Análise dos efeitos da exposição ao ambiente enriquecido sobre as alterações do metabolismo desencadeadas pelo estresse neonatal em ratos wistar(Universidade Federal de São Paulo (UNIFESP), 2018-12-05) Carvalho, Lucas Emanuel Oliveira [UNIFESP]; Castro, Glaucia Monteiro de [UNIFESP]; http://lattes.cnpq.br/2727707909050870; http://lattes.cnpq.br/3813352323717675; Universidade Federal de São Paulo (UNIFESP)Atualmente numerosos estudos fornecem evidencias de que desordens psiquiátricas, metabólicas, cardíaca e imunológica, tem sua gênese determinada pelo estresse neonatal. O estresse neonatal mediado pela ativação do eixo Hipotalâmico-Pituitária-Adrenal (HPA) promove alterações nas estruturas do sistema límbico, especialmente no hipocampo, amígdala e córtex pré-frontal. Em face às evidências de que durante os períodos perinatais a criança é um campo aberto aos diversos tipos de estímulos ambientais, hipotetizamos que os efeitos deletérios provenientes da negligência neonatal, podem ser revertidos ou atenuados com a estimulação em ambiente enriquecido (AE). O AE é especialmente planejado para estimular, as atividades sensoriais, motoras, cognitivas e de interação social entre os animais, gerando uma melhora na aprendizagem espacial, na memória e no comportamento social. O objetivo do presente trabalho foi investigar os efeitos da exposição ao ambiente enriquecido em animais submetidos ao estresse neonatal. Para tanto, foram utilizadas fêmeas Wistar prenhes, provenientes do CEDEME e após 48 horas do nascimento da prole, foram distribuídas em três grupos diferentes: controle (CTL), estresse (ES) e estresse com exposição ao ambiente enriquecido (EAE). Os animais foram pesados de dois em dois dias e foram realizados testes de atividade (actimetria), teste de campo aberto e teste de tolerância a insulina. Após a eutanásia, foram realizadas análises de perfil lipídico, análise de proteínas e gorduras de carcaça. Os testes de atividade e comportamento mostraram maior locomoção, número de cruzamentos e levantamentos dos grupos estresse e estresse AE em comparação com o grupo controle. Nossos resultados mostraram que os animais do grupo STR apresenta maior massa corpórea e o grupo STRAE o menor índice na comparação entre os grupos experimentais. A análise do perfil lipídico demonstrou que os grupos submetidos ao estresse neonatal (ES e EAE) apresentaram maiores níveis de colesterol total e LDL (lipoproteína de baixa densidade) em relação ao grupo CTL, evidenciando que o estresse tem efeitos sobre a alteração do perfil lipídico dos animais. Consistente com os resultados obtidos na massa corpórea e perfil lipídico, verificou-se que o grupo STR apresentar maior percentual de gordura em relação ao grupo estresse AE. A partir dos dados analisados, concluímos que o estresse promoveu alterações sobre o perfil lipídico, a locomoção, o comportamento e a composição corporal dos animais.
- ItemSomente MetadadadosAre endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?(Elsevier B.V., 2010-02-01) Andersen, Monica Levy [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Alvarenga, Tathiana Aparecida [UNIFESP]; Silva, Andressa [UNIFESP]; Araujo, Paula [UNIFESP]; Zager, Adriano [UNIFESP]; Tenório, Neuli Maria [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. the results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. in ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. in conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones. (c) 2009 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Avaliação da resposta de estresse em ratas submetidas ao estresse crônico e a múltiplos ciclos de superovulação(Universidade Federal de São Paulo, 2018-03-23) Gonçalves, Bianca Santos Martins [UNIFESP]; Le Sueur-Maluf, Luciana [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)It Is Estimated That Infertility Affects About 10-15% Of Couples Of Childbearing Age Within The World Population, While Annually, 7-10% Of Couples Of Reproductive Age In Brazil Rely On Services Specialized In Fertility Disorders Treatment. From A Psychosocial Perspective, Infertile Individuals Experience Intense Psychological Stress, Related To Emotional Disorders, Which Have Repercussions On Marital And Social Relationships. While The Stress Impact On The Success Of Assisted Reproduction Treatments (Art) Has Been Comprehensively Studied, The Role Of Supraphysiological Concentrations Of Gonadal Hormones (Commonly Experienced By Women In Treatment) On Stress Response, Remains To Be Elucidated. The Aim Of Study Was To Evaluate The Stress Response In Female Rats Submitted To Chronic Stress And Multiple Cycles Of Superovulation Treatment. In Order To Mimic The Context Of Art In Rodents, Female Wistar Rats (10 Weeks Old) With Proven Regular Estrous Cycle, Were Exposed To The Unpredictable Chronic Mild Stress Proto
- ItemAcesso aberto (Open Access)Avaliação dos efeitos do estresse e da administração de corticosterona em diferentes modelos de memória(Universidade Federal de São Paulo (UNIFESP), 2016-05-04) Raya, Juliana [UNIFESP]; Hipólide, Débora Cristina [UNIFESP]; http://lattes.cnpq.br/6303382961871353; http://lattes.cnpq.br/3803119831331341; Universidade Federal de São Paulo (UNIFESP)Memory can be affected by several factors, among them stress. Acute stress, depending on the moment it is applied, may facilitate or impair memory. Chronic stress may affect memory according to their duration and intensity, causing deficit, improvement or no effect. Thus, the objective of this study was to investigate the effects of chronic stress and acute and chronic administration of corticosterone (CORT) in different memory tasks in rats. First, chronic mild stress (ECB) was performed, and animals were evaluated in the Multiple Trial Inhibitory Avoidance task (EIMT). ECB induced an anhedonic behavior in rats, noticed by reduction of sucrose consumption, yet there were no changes in the EIMT performance. We suggest that sucrose may be acting as an attenuator of stress effects. In the second experiment chronic restraint stress was conducted and animals were evaluated in the Morris Water Maze task (TLAM). Rats submitted to chronic restraint stress showed better performance in TLAM than those who did not. Thus, we speculate that stress has not been enough to cause a deficit in memory, but that was moderate to facilitate performance on the task. In other experiments, CORT was administered (40 mg/kg) for 21 days by two routes: orally or subcutaneously, and animals were evaluated in TLAM. It was observed that rats which received vehicle or CORT through voluntary orally path (in a piece of bread) performed the task properly, while animals that received vehicle or CORT subcutaneously showed impairment. We suggest that this discrepancy may be related to the route of administration, since there was no drug effect on any of the experiments. We also evaluated plasmatic CORT 30 minutes after oral administration, and there was a significant increase in the concentration of CORT. Then we found no behavioral changes in the Elevated Plus Maze and Open Field after acute ingestion of CORT (10 and 40 mg/kg). We speculate that this lack of behavioral changes could be explained by the evaluation time on the tasks. In the last experiment, we evaluated the effects of subcutaneous acute administration of CORT in three moments in the EIMT task: pre-training (40 m/kg), after training (40 mg/kg) and pre-test (3, 15 and 40 mg/kg). There were no changes in the performance of animals, and we suggest that the shock employed may have been too high. Furthermore, in the EIMT task animals undergo several training sessions to reach the learning criterion, however, studies commonly use the inhibitory avoidance task with a single session. In conclusion, in this study we present a series of independent experiments that may help in the development of future work involving the effects of stress and CORT administration on memory. We also proposed a refined method of CORT oral administration, which does not present stressors and reduces animal discomfort, contributing to the ethics policy of the 3 R's.
- ItemSomente MetadadadosChronic corticosterone administration facilitates aversive memory retrieval and increases GR/NOS immunoreactivity(Elsevier B.V., 2014-07-01) Santos, Thays Brenner dos [UNIFESP]; Céspedes, Isabel Cristina [UNIFESP]; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Glucocorticoids are stress hormones that mediate the organism's reaction to stress. It has been previously proposed that the facilitation of emotional aversive conditioning induced by these hormones may involve nitric oxide-pathways. the purpose of the present study was to address this question. for that, male Wistar rats were surgically implanted with slow-release corticosterone (CORT) pellets (21 days) and tested in a step-down inhibitory avoidance task. Additional groups of animals were also submitted to the same treatment conditions and on the 21st day of treatment assayed for GR (glucocorticoid receptors)nNOS (neuronal nitric oxide synthase) immunoreactivity (GRi-nNOSi) or measurements of plasma CORT. Results showed that CORT treatment induced facilitation of step-down inhibitory avoidance. This same treatment also significantly increased CORT plasma levels and GRi in the medial, basolateral and basomedial amygdala, in the paraventricular hypothalamic nucleus (PVN), in the ventral and dorsal dentate gyrus, in the ventral CA1 region and in the dorsal CA1 and CA3 regions. Furthermore, nNOSi and GRi-nNOSi were significantly increased by CORT treatment in the medial amygdala and basolateral amygdaloid complex, in the PVN, subiculum, in the dorsal CA3 region and in the ventral CA1 and CA3 regions. These results indicate that the facilitation of aversive conditioning induced by CORT involves GR-nNOS pathways activation, what may be of relevance for a better understanding of stress-related psychiatric conditions. (C) 2014 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosChronic stress during paradoxical sleep deprivation increases paradoxical sleep rebound: Association with prolactin plasma levels and brain serotonin content(Elsevier B.V., 2008-10-01) Machado, Ricardo Borges [UNIFESP]; Tufik, Sergio [UNIFESP]; Suchecki, Deborah [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Previous studies suggest that stress associated to steep deprivation methods can affect the expression of steep rebound. in order to examine this association and possible mechanisms, rats were exposed to footshock stress during or immediately after a 96-h period of paradoxical steep deprivation (PSD) and their steep and heart rate were recorded. Control rats (maintained in individual home cages) and paradoxical steep-deprived (PS-deprived) rats were distributed in three conditions (1) no footshock - NF; (2) single footshock - SFS: one single footshock session at the end of the PSD period (6-8 shocks per minute; 100 ms; 2 mA; for 40 min); and (3) multiple footshock - MFS: footshock sessions with the same characteristics as described above, twice a day throughout PSD (at 7:00 h and 19:00 h) and one extra session before the recovery period. After PSD, animals were allowed to sleep freely for 72 h. Additional groups were sacrificed at the end of the steep deprivation period for blood sampling (ACTH, corticosterone, protactin and catecholamine levels) and brain harvesting (monoamines and metabolites). Neither SFS nor MFS produced significant alterations in the steep patterns of control rats. All PS-deprived groups exhibited increased heart rate which could be explained by increased dopaminergic activity in the medulla. As expected, PS deprivation induced rebound of paradoxical steep in the first day of recovery; however, PSD + MFS group showed the highest rebound (327.3% above the baseline). This group also showed intermediate Levels of corticosterone and the highest levels of protactin, which were positively correlated with the Length of PS episodes. Moreover, paradoxical steep deprivation resulted in elevation of the serotonergic turnover in the hypothalamus, which partly explained the hormonal results, and in the hippocampus, which appears to be related to adaptive responses to stress. the data are discussed in the realm of a prospective importance of paradoxical steep for processing of traumatic events. (C) 2008 Elsevier B.V. ALL rights reserved.
- ItemSomente MetadadadosChronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis(Elsevier B.V., 2013-08-01) Andrade, José Simões de [UNIFESP]; Céspedes, Isabel Cristina [UNIFESP]; Abrão, Renata Oliveira [UNIFESP]; Santos, Thays Brenner dos [UNIFESP]; Diniz, Leila [UNIFESP]; Britto, Luiz Roberto Giorgetti de; Spadari-Bratfisch, Regina Celia [UNIFESP]; Ortolani, Daniela [UNIFESP]; Melo-Thomas, Liana [UNIFESP]; Silva, Regina Cláudia Barbosa da [UNIFESP]; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. in unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. in stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. in stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis. (C) 2013 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosConsequences of continuous social defeat stress on anxiety- and depressive-like behaviors and ethanol reward in mice(Academic Press Inc Elsevier Science, 2018) Macedo, Giovana Camila [UNIFESP]; Morita, Gleice Midori [UNIFESP]; Domingues, Liz Paola [UNIFESP]; Favoretto, Cristiane Aparecida [UNIFESP]; Suchecki, Deborah [UNIFESP]; Hartmann Quadros, Isabel Marian [UNIFESP]This study employed the intruder-resident paradigm to evaluate the effects of continuous social defeat on depressive- and anxiety-like behaviors and the reinforcing and motivational actions of ethanol in male Swiss mice. Male Swiss mice were exposed to a 10-day social defeat protocol, while control mice cohabitated with a non aggressive animal. Continuous defeat stress consisted of episodes of defeat, followed by 24 h or 48 h cohabitation with the aggressor until the following defeat. Mice were assessed for sucrose drinking (anhedonia), social investigation test, elevated plus-maze, conditioned place preference to ethanol, and locomotor response to ethanol. Plasma corticosterone was measured prior to, after the first and the final defeat, and 10 days after the end of defeat. Defeated mice exhibited a depressive-like phenotype as indicated by social inhibition and reduced sucrose preference, relative to non-defeated controls. Defeated mice also displayed anxiety-like behavior when tested in the elevated plus-maze. Stressed animals failed to present ethanol-induced locomotor stimulation, but showed increased sensitivity for ethanol-induced conditioned place preference. Corticosterone response to defeat was the highest after the first defeat, but was still elevated after the last defeat (day 10) when compared to non stressed controls. Baseline corticosterone levels were unchanged 10 days after the final defeat. These data suggest that social defeat stress increased depressive- and anxiety-like behavior as well increased vulnerability to ethanol reward in mice.
- ItemAcesso aberto (Open Access)Contribuição do sono e da corticosterona no desempenho de ratos na tarefa de condicionamento de medo ao contexto(Universidade Federal de São Paulo (UNIFESP), 2008) Tiba, Paula Ayako [UNIFESP]; Suchecki, Deborah [UNIFESP]; Oliveira, Maria Gabriela Menezes deEstudos a respeito do papel do sono na consolidação da memória mostram que 0 estresse pode ser um fator interferente importante, uma vez que os hormônios do eixo hipotálamo-hipófise-adrenal liberados em resposta ao estresse afetam tanto 0 sono quanto a memória. 0 efeito produzido por estes hormônios e bifásico, de modo que em concentrações intermediárias, a corticosterona (CORT) pode induzir um aumento de sono e melhorar 0 desempenho de ratos em tarefas de memória, enquanto que em concentrações baixas ou altas, induzem vigília e prejudicam 0 desempenho. Diversos estudos mostram que a privação de sono prejudica 0 desempenho em tarefas de memória. Este prejuízo pode ser devido a falta de sono ou ao estresse inerente ao método de privação. Por outro lado, durante 0 aprendizado de uma tarefa aversiva, como 0 condicionamento de medo ao contexto (CMC), 0 choque nas patas pode induzir a liberação de CORT em concentrações suficientes tanto para melhorar 0 desempenho nesta tarefa quanto para induzir um aumento de sono. Desta forma, 0 estresse torna-se uma nova variável interferente no que diz respeito ao aumento de sono subseqüente ao aprendizado (que pode ocorrer pelo aprendizado per se ou pelo estresse). Portanto, no presente projeto, investigou-se a influência da CORT sobre 0 sono e a memória por meio de duas abordagens: 1) bloqueando sua síntese durante a privação de sono e avaliando 0 desempenho de animais na tarefa de CMC; e 2) acompanhando a resposta de CORT e 0 padrão de sono de animais durante a aquisição e a extinção da tarefa de CMC, em um protocolo que envolve a apresentação e a retirada do estímulo aversivo, o choque nas patas. Na primeira etapa demonstrou-se que 0 prejuízo de memória em animais privados de sono não se deve à elevação das concentrações plasmáticas de CORT, uma vez que 0 bloqueio da síntese deste hormônio pela metirapona não impediu que os animais apresentassem desempenho prejudicado. Na segunda etapa verificou-se que após o treino e evocação na tarefa de CMC, ocorreu aumento na concentração de CORT. Ao longo do procedimento de extinção, juntamente com a redução na resposta comportamental de medo dos animais, a liberação de CORT encontrou-se diminuída. Desta forma, este protocolo mostrou-se útil para a avaliação do padrão de sono na vigência de concentrações reduzidas de CORT durante 0 registro de sono subseqüente. Os resultados mostraram que existe um aumento de sono ao longo do processo de extinção, que, entretanto, também ocorreu com 0 passar do tempo para 0 grupo controle. Assim, as alterações de sono não seguem a liberação hormonal, levando à conclusão que o aumento de sono após o aprendizado não se deve à liberação de corticosterona. De forma geral, concluímos que os glicocorticóides não são responsáveis pelo prejuízo de memória em animais privados de sono, nem pelo aumento de sono decorrente do aprendizado..
- ItemSomente MetadadadosDieta rica em ácidos graxos polinsaturados n-6: influência sobre a liberação basal de mediadores inflamatórios(Universidade Federal de São Paulo (UNIFESP), 2005) Xavier, Roberta Araújo Navarro [UNIFESP]; Silveira, Vera Lucia Flor [UNIFESP]Mudanças nos ácidos graxos da dieta podem provocar alterações na fluidez e na composição dos fosfolipídios de membrana, alterando a produção de importantes mediadores e moduladores inflamatórios. Nesse sentido, demonstramos anteriormente que animais alimentados por 7 semanas com dietas ricas em ácidos graxos poliinsaturados (AGP) apresentaram redução da resposta inflamatória aguda, que foi parcialmente atribuída aos elevados níveis basais de corticosterona observados. Adicionalmente, observamos que esse efeito antiinf1amatório foi acompanhado por alterações nos níveis de fibrinogênio, leptina, bradicinina e citocinas pró e antiinflamatórias. Não se sabe, porém, se na ausência de estímulo inflamatório as dietas lipídicas, ricas em AGP, poderiam alterar por si só, o nível desses mediadores. Este trabalho avaliou o efeito da dieta rica em AGP n-6 sobre a liberação basal de corticosterona, fibrinogênio, leptina sérica, bradicinina e citocinas (Interleucinas lL-l, IL-4, IL-6,IL-10) em ratos alimentados por 4, 5, 6, ou 7 semanas. A dieta rica em AGP n-6 não alterou os níveis basais de bradicinina e citocinas, mas aumentou a concentração basal de corticosterona, leptina e fibrinogênio. Esses dados sugerem uma relação entre essas alterações e o efeito antiinflamatório dessa dieta observado na 5a, 6a e 7a semana de alimentação, já que os mediadores alterados podem agir como modula dores da resposta inflamatória.
- ItemAcesso aberto (Open Access)Different stress modalities result in distinct steroid hormone responses by male rats(Associação Brasileira de Divulgação Científica, 2004-06-01) Andersen, Monica Levy [UNIFESP]; Bignotto, Magda [UNIFESP]; Machado, Ricardo Borges [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Since both paradoxical sleep deprivation (PSD) and stress alter male reproductive function, the purpose of the present study was to examine the influence of PSD and other stressors (restraint, electrical footshock, cold and forced swimming, N = 10 per group) on steroid hormones in adult Wistar male rats. Rats were submitted to chronic stress for four days. The stressors (footshock, cold and forced swimming) were applied twice a day, for periods of 1 h at 9:00 and 16:00 h. Restrained animals were maintained in plastic cylinders for 22 h/day whereas PSD was continuous. Hormone determination was measured by chemiluminescent enzyme immunoassay (testosterone), competitive immunoassay (progesterone) and by radioimmunoassay (corticosterone, estradiol, estrone). The findings indicate that PSD (13.7 ng/dl), footshock (31.7 ng/dl) and cold (35.2 ng/dl) led to lower testosterone levels compared to the swimming (370.4 ng/dl) and control (371.4 ng/dl) groups. However, progesterone levels were elevated in the footshock (4.5 ng/ml) and PSD (5.4 ng/ml) groups compared to control (1.6 ng/ml), swimming (1.1 ng/ml), cold (2.3 ng/ml), and restrained (1.2 ng/ml) animals. Estrone and estradiol levels were reduced in the PSD, footshock and restraint groups compared to the control, swimming and cold groups. A significant increase in corticosterone levels was found only in the PSD (299.8 ng/ml) and footshock (169.6 ng/ml) groups. These changes may be thought to be the full steroidal response to stress of significant intensity. Thus, the data suggest that different stress modalities result in distinct steroid hormone responses, with PSD and footshock being the most similar.
- ItemSomente MetadadadosDistinct effects of acute and chronic sleep loss on DNA damage in rats(Elsevier B.V., 2009-04-30) Andersen, Monica Levy [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Bergamaschi, Cassia Toledo [UNIFESP]; Alvarenga, Tathiana Aparecida [UNIFESP]; Silva, Andressa [UNIFESP]; Zager, Adriano [UNIFESP]; Campos, Ruy Ribeiro [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. the results showed DNA damage in blood cells of rats submitted to PSD for 96 h. Brain tissue showed extensive genotoxic damage in PSD rats (both 24 and 96 h), though the effect was more pronounced in the 96 h group. Rats allowed to recover from the PSD-96 h and SR-21 days treatments showed DNA damage as compared to negative controls. Liver and heart did not display any genotoxicity activity. Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation. (C) 2009 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Efeito do tratamento com escitalopram sobre as alterações emocionais decorrentes do estresse neonatal em ratos Wistar adolescentes machos e fêmeas e as consequências de manipulações no período neonatal sobre o comportamento materno(Universidade Federal de São Paulo (UNIFESP), 2018-04-26) Zanta, Natalia Cristina [UNIFESP]; Suchecki, Deborah [UNIFESP]; Girardi, Carlos Eduardo Neves; http://lattes.cnpq.br/0014777128958249; http://lattes.cnpq.br/0735654567907174; http://lattes.cnpq.br/3963714101668953; Universidade Federal de São Paulo (UNIFESP)Early life adversities may lead to long-term behavioural and hormonal changes, due to immaturity of the central nervous system, resulting in increased vulnerability to stressful events. In rodents, there is a developmental phase, between postnatal days (PNDs) 4 and 14, characterized by low corticosterne stress reactivity, the stress hyporesponsive period (SHRP). Maternal deprivation (DEP) on PND 9, leads to altered depressive- and anxiety-like behaviours, in addition to unbalanced serotoninergic activity, in adolescent and adult male and female rats. In the present study, we tested the hypothesis that chronic treatment with escitalopram (ESC), the most specific selective serotonin reuptake inhibitor, would normalize these altered behaviours. To this end, whole litters were standardized to four males and four females, and either kept with their mother throughout development (control, CTL) or DEP on PND 9 (DEP9). On PND 10, 2 h before the end of the deprivation period or at the appropriate time for CTL pups, half of the total number of litters in each group received a saline injection (SAL stress) or not (NSAL), making up for the four main groups: CTL-NSAL, CTL-SAL, DEP9-NSAL, DEP9-SAL. Following these procedures, litters were reunited with their mothers and maternal behaviour was assessed 3 times during PND 10, at 10:00 h, 14:00 h and 17:30 h. Weaning took place on PND 21, and administration of vehicle (2 males and 2 females) or ESC (2 males and 2 females) began and lasted for 24 days; treatment was the intra-litter variable. After 21 days of treatment, 1 male and 1 female in each treatment were non-tested (basal corticosterone levels) and the other animals were submitted to several tests of emotionality, without interruption of the pharmacological treatment. Immediately after the last test, blood samples were taken for determination of corticosterone stress levels. The results showed that DEP9, alone or in combination with SAL increased maternal behaviour. Neonatal manipulations did not change parameters in the open field test but were anxyogenic for females in the elevated plus maze. ESC increased social investigation only in males and SAL produced a pro-depressive effect in the forced swimming test in males. The behavioural tests elicited a corticosterone response in males, but not in females. Based on these results we conclude that neonatal manipulations increased maternal behaviour and that alterations in late adolescence were sex-dependent. The pharmacological treatment produced a positive effect only in the social investigation test and, therefore, was not effective in improving the behavioural changes induced by maternal deprivation.
- ItemSomente MetadadadosEfeitos da corticosterona sobre o comportamento de ratos no modelo da transição claro/escuro e sobre a imunorreatividade à proteína Delta-FOSB em áreas encefálicas, relacionadas à modulação do estresse e da ansiedade(Universidade Federal de São Paulo (UNIFESP), 2017-05-11) Hirata, Rafael Yutaka Scalize [UNIFESP]; Viana, Milena de Barros [UNIFESP]; http://lattes.cnpq.br/3053794724319601; Universidade Federal de São Paulo (UNIFESP)The concept of stress is based on the observation that different types of environmental changes (external or internal) can threaten the homeostasis / allostasis of the organism, leading to a set of bodily changes that characterize the "general adaptation syndrome". In this sense, the term stress can be used both to identify events or circumstances that are perceived as aversive (stressors) and to describe a state induced by stressors (stress reaction). The goal of the latter is to maintain homeostasis / alostase, which includes a series of physiological responses such as endocrine and cardiovascular activation, which in themselves do not produce pathological changes. However, when aversive stimulation occurs for a prolonged period or exceeds the body's ability to maintain homeostasis / alostase, stress can lead to pathological sequelae. The objective of the present study was to investigate the effects of chronic corticosterone glucocorticoid treatment (CORT) on behavior (anxiety and locomotion) and neuronal activation pattern in areas related to stress modulation. Male Wistar rats(8 weeks) were submitted to CORT treatment (21 days, 200 mg slow release pellets) and were then tested in the light / dark transition model and open field. After the tests, the animals were euthanized and their brains processed for deltaFosB-ir analysis. The results obtained in the present study showed that the chronic treatment with CORT decreased the number of rearings in the open field model without altering the number of crossings or the anxiety measurements performed in the light/dark transition model. The data from the immunohistochemical analysis showed that different brain structures related to the modulation of the stress and motor behavior were activated by the chronic treatment with CORT: The cingulate cortex; The dorsolateral and ventrolateral septum; The central, medial, basolateral, basomedial and lateral amygdala; The paraventricular, dorsomedial and ventromedial hypothalamus; The dorsomedial, dorsolateral, lateral and ventrolateral periaquedutal gray matter; And the dorsal, lateral and ventral wings of the dorsal nucleus of the raphe and the median nucleus of the raphe. These results contribute to a better understanding of the effects of chronic treatment with CORT.
- ItemAcesso aberto (Open Access)Efeitos da privação materna no dia 11, associada a um estressor pontual, sobre a emocionalidade e monoaminas cerebrais em ratos Wistar machos e fêmeas adultos(Universidade Federal de São Paulo (UNIFESP), 2017-09-28) Cabbia, Rafael [UNIFESP]; Suchecki, Deborah [UNIFESP]; http://lattes.cnpq.br/0735654567907174; http://lattes.cnpq.br/3927520743783767; Universidade Federal de São Paulo (UNIFESP)A privação materna (PM) por 24 horas durante o período de hiporresponsividade ao estresse desinibe as glândulas adrenais do neonato, tornando-as aptas a liberarem altas concentrações de corticosterona em resposta a estímulos estressores. Um estresse pontual e brando, como uma injeção de salina, produz secreção de corticosterona intensa e sustentada, por pelo menos 2 h, apenas em neonatos submetidos à PM. Assim, testamos a hipótese de que um estresse (injeção de salina), 2 h antes do término da PM imposta no dia pós-natal (DPN) 11 poderia alterar os comportamentos do tipo-ansioso, depressivo e social, resposta de estresse e monoaminas cerebrais de ratos machos e fêmeas na idade adulta. O comportamento maternal também foi avaliado em três horários após a reunião das ninhadas com suas mães ou após o estresse pontual. Os animais foram testados no novelty-suppressed feeding, testes de contraste positivo e negativo de sacarose, investigação social e labirinto em cruz elevado (LCE). Amostras de sangue foram coletadas em diferentes intervalos de tempo após o LCE para a determinação das concentrações plasmáticas de corticosterona (CORT). Uma quarta parte dos animais não foi testada, fornecendo amostras basais para as concentrações de CORT e de monoaminas cerebrais analisadas no hipotálamo (HPT), córtex frontal (CF), amígdala (AMG), hipocampo ventral (HV) e dorsal (HD). Os resultados mostraram que a PM produziu aumento mais robusto sobre os comportamentos maternos (principalmente logo após a reunião das ninhadas com suas mães) do que a injeção de salina. Na idade adulta, os animais submetidos à PM independente do sexo, apresentaram redução do comportamento alimentar e alteração do comportamento ansioso no novelty-suppressed feeding, representado pela menor latência para consumo de alimento durante o teste. A injeção de salina interagiu com a PM produzindo redução da exploração do rato-alvo no teste de investigação social, independente do sexo. Em relação à resposta de estresse após o LCE, a privação materna aumentou a magnitude da liberação de CORT em machos e fêmeas, contudo, a injeção de salina apresentou efeito apenas em fêmeas, demonstrado pela maior magnitude da resposta quando comparada aos animais que não receberam salina. Por fim, as manipulações neonatais produziram efeitos sobre as concentrações de monoaminas cerebrais em condições basais: em fêmeas a PM diminuiu as concentrações de dopamina na AMG e aumentou as concentrações de noradrenalina no CF, enquanto que a injeção de salina diminuiu as concentrações de serotonina no HPT. Em machos, a PM acarretou efeitos apenas no sistema serotoninérgico, reduzindo suas concentrações no córtex e no hipotálamo. Em contrapartida, a PM e a injeção de salina interagiram produzindo alterações nas concentrações de dopamina na AMG, CF, HV e HD. Concluímos, portanto, que apenas a PM induz um aumento de dois comportamentos maternais de forma pontual: o ABN e LGA. A privação materna no DPN 11 não produziu efeitos sobre o comportamento ansioso, depressivo e social, mas afetou a resposta de estresse. A injeção de salina durante a privação afetou notavelmente a resposta de estresse de animais de ambos os sexos, bem como interagiu com a privação causando alterações dopaminérgicas em machos. Estes resultados demonstram, portanto, que um desafio brando durante o período neonatal pode causar alteração na programação biológica da resposta de estresse, e que, caso este desafio seja enfrentado durante a ausência de cuidados maternais, ocasiona alteração na disponibilidade de dopamina no cérebro de machos, mas não de fêmeas – sugerindo um claro dimorfismo sexual.
- ItemSomente MetadadadosEfeitos do enriquecimento ambiental sobre o comportamento de ansiedade e pânico em ratos e substratos neurais envolvidos(Universidade Federal de São Paulo (UNIFESP), 2018-12-13) Lopes, Danielle Abreu [UNIFESP]; Viana, Milena de Barros [UNIFESP]; http://lattes.cnpq.br/3053794724319601; Universidade Federal de São Paulo (UNIFESP)Environmental Enrichment (Ee) Is An Animal Management Technique That Offers A Series Of Stimuli Which Seems To Improve Adaptation To The Conditions Of Housing In Captive Animals. The Anxiolytic Effects Produced By Ea Are Still Unclear. In Fact, Ea Ahas Been Proposed As A Mild Stressor Agent. To Better Understand The Relationship Between Ea And Anxiety-Related Disorders, A Simple Ea Procedure Was Developed In The Present Study To Be Used In Research Areas. After That, The Study Exposed Wistar Rats During One And Two Weeks Of Ea And Subsequently Tested These Animals In The Inhibitory Avoidance And Escape Tasks Of The Elevate T Maze (Etm) Model Of Anxiety. In Clinical Terms, These Responses Are Related To Generalized Anxiety And Panic Disorder, Respectively. Immediately After The Etm, All Animals Were Tested In The Open Field To Evaluated Locomotor Activity. An Immunohistochemical Study Was Performed To Analyse Delta Fosb Protein Immunoreactivity (Fosb-Ir) In Stress / Anxiety Related Brain Areas, As Well As Doub
- ItemRestritoEfeitos do estresse agudo repetido sobre o desempenho locomotor de rãs Lithobates catesbeianus (Anura, Ranidae)(Universidade Federal de São Paulo, 2022-01-22) Milan, Júlia [UNIFESP]; Carvalho, José Eduardo de [UNIFESP]; http://lattes.cnpq.br/6738085765102617; http://lattes.cnpq.br/4071630543802340Em vertebrados ectotérmicos, a resposta ao estresse é bastante variada e depende essencialmente do tipo e da intensidade do agente estressor. Apesar da resposta ao estresse agudo ser vantajosa por preparar o organismo para enfrentar uma determinada situação, a continuidade prolongada do estímulo ou sua repetição pode ser prejudicial. Em anuros, por exemplo, o estresse agudo repetitivo prejudica o desempenho da resposta imune e, consequentemente, da capacidade do animal em combater agentes inflamatórios. Ainda em anuros, os efeitos do estresse repetitivo podem comprometer outras funções como a digestória e a reprodutiva. Para compreender melhor os efeitos do estresse agudo repetido sobre aspectos fisiológicos de anuros, verificamos neste trabalho suas consequências sobre a atividade locomotora. Simulamos a resposta fisiológica ao estresse agudo através da aplicação transdermal de corticosterona, feita diariamente em rãs-touro Lithobates catesbeianus. Utilizamos a velocidade de deslocamento em água e solo como proxy do desempenho locomotor. Em linhas gerais, a aplicação transdermal de corticosterona por 13 dias não afetou a velocidade de deslocamento na natação. Também observamos que após 29 dias de tratamento a velocidade de deslocamento por saltos não foi afetada. Ao final verificamos que o tratamento de estresse agudo repetido não causou efeito no desempenho locomotor das rãs-touro.
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