Expressão de receptores de melatonina em um modelo animal com aumento na interação social
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Data
2019-04-25
Autores
Vieira, Isis Zion [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Introdução: Áreas encefálicas como hipocampo, hipotálamo, cerebelo e o córtex pré-frontal participam do controle de habilidades sociais fundamentais para a saúde e o bem-estar. Alterações bioquímicas nestas áreas podem alterar a expressão do comportamento social em quadros patológicos como depressão, esquizofrenia, distúrbios bipolares e em transtornos do neurodesenvolvimento. Esclarecer os mecanismos envolvidos nessas alterações é essencial para o desenvolvimento de ações terapêuticas nestes quadros. Estudos recentes mostraram que a melatonina e seu agonista agomelatina podem estar envolvidos na modulação do comportamento social principalmente por meio dos receptores MT1 e MT2. Porém, pouco se sabe sobre variações no conteúdo de melatonina e na expressão destes receptores em diferentes áreas encefálicas, em quadros que apresentam alterações no comportamento social. Objetivos: Avaliar a concentração plasmática de melatonina, a expressão gênica dos receptores de melatonina MT1 e MT2 em diferentes áreas encefálicas, e a localização e quantificação das células imunorreativas para MT1 e MT2 no córtex pré-frontal de modelo animal com aumento na interação social. Métodos: Amostras de sangue e de tecido encefálico foram obtidas de ratos com aumento na interação social (grupo mais social) e ratos com interação social considerada normal para a espécie (grupo controle). Com o intuito de confirmar as diferenças no comportamento de interação social entre os dois grupos, todos os animais passaram por avaliação comportamental. A melatonina plasmática foi quantificada por ELISA; a expressão gênica dos receptores MT1 e MT2 no córtex pré-frontal, hipocampo, hipotálamo e cerebelo foi analisada por PCR em tempo real e a localização dos receptores MT1 e MT2 foi analisada por imunohistoquímica. Resultados: Os testes comportamentais mostraram que o grupo mais social apresentou maior tempo de interação social e menor tempo e frequência de limpar-se em relação ao grupo controle. O grupo mais social apresentou menor concentração plasmática de melatonina que o grupo controle e maior expressão dos RNAm de MT1 no hipotálamo, hipocampo, pré-frontal e cerebelo, e maior expressão dos RNAm de MT2 no hipotálamo, hipocampo e cerebelo. O grupo mais social apresentou maior número de células imunorreativas para MT1 na área total do córtex pré-frontal e nas divisões LO, MO, VO, PrL. Não houve diferença na imunorreatividade para o receptor MT2 entre os grupos mais social tanto na área total quanto nas divisões do córtex pré-frontal. Conclusão: Os animais da linhagem mais social apresentaram maior interação social com o co-específico do que o grupo controle, menor conteúdo de melatonina, maior expressão gênica dos receptores de melatonina MT1 no hipocampo, hipotálamo, córtex pré-frontal e cerebelo, e do MT2 no hipocampo, hipotálamo e cerebelo. Além disso a linhagem mais social apresentou maior número de células imunorreativas ao receptor de melatonina MT1 no córtex pré-frontal.
Introduction: Encephalic areas such as the hippocampus, hypothalamus, cerebellum, and prefrontal cortex participate in the control of social skills fundamental to health and well-being. Biochemical changes in these areas may alter the expression of social behavior in pathological conditions such as depression, schizophrenia, bipolar disorders and neurodevelopmental disorders. Clarifying the mechanisms involved in these changes is essential for the development of therapeutic actions in these frameworks. Recent studies have shown that melatonin and its agonist agonist may be involved in the modulation of social behavior mainly through the MT1 and MT2 receptors. However, little is known about variations in the content of melatonin and the expression of these receptors in different brain areas, in pictures that present changes in social behavior. Objectives: To evaluate the plasma concentration of melatonin, the gene expression of MT1 and MT2 melatonin receptors in different brain areas, and the localization and quantification of MT1 and MT2 immunoreactive cells in the animal model prefrontal cortex with increased social interaction. Methods: Blood and brain tissue samples were obtained from rats with increased social interaction (more social group) and rats with social interaction considered normal for the species (control group). In order to confirm the differences in behavior of social interaction between the two groups, all animals underwent behavioral evaluation. Plasma melatonin was quantified by ELISA; the gene expression of MT1 and MT2 receptors in the prefrontal cortex, hippocampus, hypothalamus and cerebellum was analyzed by real-time PCR and the location of MT1 and MT2 receptors was analyzed by immunohistochemistry. Results: Behavioral tests showed that the most social group had an increase in social interaction time and a decrease in the time and frequency of cleansing in relation to the control group. The more social group presented lower plasma concentration of melatonin than the control group and higher expression of MT1 mRNAs in the hypothalamus, hippocampus, prefrontal and cerebellum, and higher expression of MT2 mRNAs in the hypothalamus, hippocampus and cerebellum. The most social group had a higher number of MT1 immunoreactive cells in the LO, MO, VO, PrL and total prefrontal cortex areas, and there was no greater immunoreactivity for the MT2 receptor in the subareas and in the total area of the pre- front. Conclusion: The animals of the more social line presented greater social interaction with the co-specific than the control group. These animals had lower melatonin content, greater gene expression of MT1 melatonin receptors in the hippocampus, hypothalamus, prefrontal cortex and cerebellum, and MT2 in the hippocampus, hypothalamus and cerebellum. In addition, a larger number of MT1 melatonin receptor immunoreactive cells were present in the PrL, MO, VO and LO subdivisions of the prefrontal cortex.
Introduction: Encephalic areas such as the hippocampus, hypothalamus, cerebellum, and prefrontal cortex participate in the control of social skills fundamental to health and well-being. Biochemical changes in these areas may alter the expression of social behavior in pathological conditions such as depression, schizophrenia, bipolar disorders and neurodevelopmental disorders. Clarifying the mechanisms involved in these changes is essential for the development of therapeutic actions in these frameworks. Recent studies have shown that melatonin and its agonist agonist may be involved in the modulation of social behavior mainly through the MT1 and MT2 receptors. However, little is known about variations in the content of melatonin and the expression of these receptors in different brain areas, in pictures that present changes in social behavior. Objectives: To evaluate the plasma concentration of melatonin, the gene expression of MT1 and MT2 melatonin receptors in different brain areas, and the localization and quantification of MT1 and MT2 immunoreactive cells in the animal model prefrontal cortex with increased social interaction. Methods: Blood and brain tissue samples were obtained from rats with increased social interaction (more social group) and rats with social interaction considered normal for the species (control group). In order to confirm the differences in behavior of social interaction between the two groups, all animals underwent behavioral evaluation. Plasma melatonin was quantified by ELISA; the gene expression of MT1 and MT2 receptors in the prefrontal cortex, hippocampus, hypothalamus and cerebellum was analyzed by real-time PCR and the location of MT1 and MT2 receptors was analyzed by immunohistochemistry. Results: Behavioral tests showed that the most social group had an increase in social interaction time and a decrease in the time and frequency of cleansing in relation to the control group. The more social group presented lower plasma concentration of melatonin than the control group and higher expression of MT1 mRNAs in the hypothalamus, hippocampus, prefrontal and cerebellum, and higher expression of MT2 mRNAs in the hypothalamus, hippocampus and cerebellum. The most social group had a higher number of MT1 immunoreactive cells in the LO, MO, VO, PrL and total prefrontal cortex areas, and there was no greater immunoreactivity for the MT2 receptor in the subareas and in the total area of the pre- front. Conclusion: The animals of the more social line presented greater social interaction with the co-specific than the control group. These animals had lower melatonin content, greater gene expression of MT1 melatonin receptors in the hippocampus, hypothalamus, prefrontal cortex and cerebellum, and MT2 in the hippocampus, hypothalamus and cerebellum. In addition, a larger number of MT1 melatonin receptor immunoreactive cells were present in the PrL, MO, VO and LO subdivisions of the prefrontal cortex.
Descrição
Palavras-chave
Comportamento social, Melatonina, Receptores de melatonina, Córtex pré-frontal, Social behavior, Melatonin, Melatonin receptors, Prefrontal cortex