Ativação serotonérgica e não-serotonérgica nos núcleos mediano e dorsal da rafe, nas diferentes fases do ciclo estral de ratas e após ovariectomia
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Data
2018-03-07
Autores
Batistela, Matheus Fitipaldi
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Universidade Estadual Paulista (Unesp)
Resumo
Deakin e Graeff propuseram que ansiedade e o pânico seriam regulados pela serotonina ou 5-hidroxitriptamina (5-HT), possuindo mais de um mecanismo de controle. Ambos os mecanismos têm sua origem nos núcleos Dorsal da Rafe (NDR) e Mediano da Rafe (NMR). O NDR possui ainda, cinco diferentes subnúcleos ao longo do eixo rostrocaudal: dorsal (DRD), ventral (DRV), lateral/asas laterais (lwDR), caudal (DRC) e interfascicular (DRI), sendo que os subnúcleos DRC, DRD e DRI originam a via modulatória do transtorno de ansiedade generalizada e o subnúcleo lwDR origina a via modulatória do transtorno do pânico. Sabe-se que as mulheres são mais suscetíveis à manifestação dos transtornos de ansiedade e de pânico do que os homens. Estudos com modelos animais de ansiedade mostram que nas fases do ciclo hormonal onde ocorre maior liberação de estrógeno, proestro e estro, é constatada ansiólise. De maneira oposta em animais na fase de metaestro e diestro, nas quais há baixa concentração sérica de estradiol, os comportamentos defensivos observados apontam para o aumento da ansiedade. Receptores para estrógeno, alfa (ERα) e beta (ERβ), foram encontrados em estruturas encefálicas descritas por Deakin e Graeff como relacionadas com a manifestação dos transtornos de ansiedade e co-localizadas em receptores serotonérgicos. Assim, esse estudo teve por objetivo avaliar a expressão de neurônios serotonérgicos e não-serotonérgicos no NMR e nos diferentes subnúcleos do NDR em relação a fase do ciclo estral de ratas e após a ovariectomia bilateral. As fêmeas foram perfundidas e os encéfalos foram processados a fim de se realizar o processo de imunohistoquímica de dupla-marcação para a proteína c-Fos (marcador indireto de ativação celular) e da enzima triptofano hidroxilase (TPH – presente somente em neurônios serotonérgicos). Não se constatou qualquer diferença quando se analisou o NMR. Os resultados encontrados mostraram um maior número de neurônios serotonérgicos e não-serotonérgicos ativados na fase de proestro, principalmente nos subnúcleos Dorsal (DRD) e Caudal (DRC). Enquanto que na fase de diestro e após ovariectomia bilateral os resultados apontaram um menor número na expressão de TPH nos subnúcleos DRD, Ventral (DRV) e DRC. Os resultados encontrados são compatíveis com achados anteriores que indicam que os subnúcleos dorsal e caudal são responsáveis pela modulação de comportamentos defensivos relacionados à ansiedade. Como houve diferença na ativação das estruturas ao longo do ciclo estral conclui-se que a presença de hormônios sexuais, principalmente o estradiol, é responsável por essas alterações observadas.
Deakin and Graeff proposed that anxiety and panic would be regulated by serotonin or 5-hydroxytryptamine (5-HT), having more than one control mechanism. Both mechanisms have their origin in Dorsal Raphe Nucleus (DRN) and Median Raphe Nucleus (MRN). The DRN also has five sub-regions along the rostrocaudal axis: dorsal (DRD), ventral (DRV), lateral / lateral wings (lwDR), caudal (DRC) and interfascicular (DRI), being that the DRC, DRD and DRI subnuclei originate the modulatory pathway of generalized anxiety disorder and the subnucleus lwDR originates the modulatory pathway of panic disorder. It is known that women are more susceptible to the manifestation of anxiety and panic disorders than men. Studies with animal models of anxiety show that in the phases of the hormonal cycle where estrogen release occurs, like proestrus and estrous, anxiolysis is observed. On the other hand, animals in the metaestrus and diestrus phase, in which there is a low concentration of estradiol, the observed defensive behaviors point to an increase in anxiety. Receptors for estrogen, alpha (ERα) and beta (ERβ) were found in structures described by Deakin and Graeff as re lated to a manifestation of anxiety disorders and co-localized in serotonergic receptors. Thus, this study aimed to evaluate the expression of serotonergic and non-serotonergic neurons in the MRN and in the different NDR subnuclei in relation to the phases of estrous cycle of rats and after a bilateral ovariectomy. The females were perfused and the brains were processed in order to perform the double-label immunohistochemistry process for c-Fos protein (cellular activation indirect marker) and tryptophan hydroxylase (TPH - present only in serotonergic neurons). No difference was found when MRN was analyzed. The results showed a higher number of serotonergic and non-serotonergic neurons activated in the proestrus phase, mainly in the Dorsal (DRD) and Caudal (DRC) subnuclei. While in the late diestrus phase and after bilateral ovariectomy the results indicated a lower number of TPH expression in the sub-nuclei DRD, Ventral (DRV) and DRC. The results are compatible with previous findings that have shown the responsible of dorsal and caudal subnuclei in the modulation of defensive behaviors related to anxiety. As there was a difference in the activation of the structures during the estrous cycle it was concluded that the presence of sex hormones, mainly estradiol, is responsible for these observed changes
Deakin and Graeff proposed that anxiety and panic would be regulated by serotonin or 5-hydroxytryptamine (5-HT), having more than one control mechanism. Both mechanisms have their origin in Dorsal Raphe Nucleus (DRN) and Median Raphe Nucleus (MRN). The DRN also has five sub-regions along the rostrocaudal axis: dorsal (DRD), ventral (DRV), lateral / lateral wings (lwDR), caudal (DRC) and interfascicular (DRI), being that the DRC, DRD and DRI subnuclei originate the modulatory pathway of generalized anxiety disorder and the subnucleus lwDR originates the modulatory pathway of panic disorder. It is known that women are more susceptible to the manifestation of anxiety and panic disorders than men. Studies with animal models of anxiety show that in the phases of the hormonal cycle where estrogen release occurs, like proestrus and estrous, anxiolysis is observed. On the other hand, animals in the metaestrus and diestrus phase, in which there is a low concentration of estradiol, the observed defensive behaviors point to an increase in anxiety. Receptors for estrogen, alpha (ERα) and beta (ERβ) were found in structures described by Deakin and Graeff as re lated to a manifestation of anxiety disorders and co-localized in serotonergic receptors. Thus, this study aimed to evaluate the expression of serotonergic and non-serotonergic neurons in the MRN and in the different NDR subnuclei in relation to the phases of estrous cycle of rats and after a bilateral ovariectomy. The females were perfused and the brains were processed in order to perform the double-label immunohistochemistry process for c-Fos protein (cellular activation indirect marker) and tryptophan hydroxylase (TPH - present only in serotonergic neurons). No difference was found when MRN was analyzed. The results showed a higher number of serotonergic and non-serotonergic neurons activated in the proestrus phase, mainly in the Dorsal (DRD) and Caudal (DRC) subnuclei. While in the late diestrus phase and after bilateral ovariectomy the results indicated a lower number of TPH expression in the sub-nuclei DRD, Ventral (DRV) and DRC. The results are compatible with previous findings that have shown the responsible of dorsal and caudal subnuclei in the modulation of defensive behaviors related to anxiety. As there was a difference in the activation of the structures during the estrous cycle it was concluded that the presence of sex hormones, mainly estradiol, is responsible for these observed changes
Descrição
Palavras-chave
Ansiedade, Fêmeas, Neurônios, Núcleo Dorsal da Rafe, Núcleo Mediano da Rafe, Estrógeno, Ciclo Estral, c-Fos, Imunohistoquímica, Triptofano Hidroxilase