Análise da expressão de genes receptores e reguladores de neurotransmissores em um novo modelo animal para esquizofrenia
Arquivos
Data
2012
Autores
Santoro, Marcos Leite 
Orientadores
Belangero, Sintia Iole
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Recentemente, nosso grupo mostrou que a linhagem Spontaneously Hypertensive Rats (SHR) apresentava uma serie de comportamentos, classicamente, associados com modelos animais de esquizofrenia. O presente projeto propoe investigar se ha diferenca na expressao de genes de receptores e reguladores de neurotransmissores no tecido sanguineo e duas regioes cerebrais (nucleus accumbens - NAcc e cortex pre-frontal - CPF) entre a linhagem de ratos SHR (N=8), modelo de esquizofrenia, e a linhagem de ratos Wistar, linhagem controle, (N=8), ambos tratados com veiculo, e entre os grupos SHR tratado e nao tratado com antipsicoticos (risperidona u N=8, clozapina u N=7, haloperidol u N=7). Nos utilizamos a tecnica de PCRarray para verificar a expressao de 84 genes relacionados a neurotransmissao. Na comparacao entre as linhagens SHR e Wistar encontramos quatro genes diferencialmente expressos no CPF (Chrnb4, Gad2, Qrfpr e Slc5a7) e um no sangue (Sstr4). Alem disso, observamos que o gene Tacr3 apresenta uma expressao diminuida no CPF e aumentada no NAcc do SHR em relacao ao Wistar e que esse gene esta correlacionado positivamente entre o sangue e NAcc e negativamente entre o sangue e CPF dos animais SHR. Com relacao aos grupos tratados com antipsicotico, encontramos tres genes diferencialmente expressos no CPF do grupo clozapina (Drd2, Drd3 e Brs3) e dois no CPF do grupo haloperidol (Brs3 e Sstr4). Nosso trabalho apontou genes diferencialmente expressos entre as duas linhagens que estao envolvidos em importantes vias relacionadas a esquizofrenia, como o Gad2 e o Tacr3, esse ultimo, um potencial biomarcador para a condicao do SHR. A comparacao entre os grupos SHR nao tratado e tratado com antipsicoticos apontou genes, possivelmente, relacionados ao efeito do antagonismo de receptores D2-like e associados a melhora no comportamento, como observado por nos anteriormente. Estes resultados demonstram semelhancas geneticas com a esquizofrenia nessa linhagem, alem de apontar um potencial biomarcador e novos genes, possivelmente, envolvidos com o fenotipo do SHR e comresposta aos antipsicoticos
Recently, our group demonstrated that Spontaneously Hypertensive Rats (SHR) strain presents a behavioral profile, classically, associated with schizophrenia animal models. The aim of this study was to characterize the expression of neurotransmitter receptors and regulators genes in brain regions (nucleus accumbens – NAcc and prefrontal cortex - CPF) and peripheral blood between SHR (N=8) and Wistar rats (control strain) (N=8), and between SHR animals treated or not with antipsychotic drugs (risperidone – N=8, clozapine – N=7, haloperidol – N=7). We used the PCRarray technology, which verifies the gene expression of 84 genes simultaneously. In the comparison between SHR and Wistar strains we found 4 genes differentially expressed in CPF (Chrnb4, Gad2, Qrfpr e Slc5a7) and one in peripheral blood (Sstr4). We also observed that the gene expression of Tacr3 in peripheral blood of SHR was positively correlated with NAcc and negatively with CPF of SHR animals. Concerning the treatment, we found three genes differentially expressed in CPF of SHR group treated with clozapine (Drd2, Drd3 e Brs3) and two in SHR group treated with haloperidol (Brs3 e Sstr4). In this study, we encountered genes differentially expressed between SHR and Wistar that are involved in important pathways of schizophrenia, such as Gad2 and Tacr3, and the latter, also correlated between blood and brain, suggesting a potential biomarker of SHR condition. In the treatment groups, we found genes probably altered due to the antagonism of D2-like receptors, and genes that can be associated with behavioral improvements after antipsychotic treatment, described previously by our group. In conclusion, our study revealed that SHR strain exhibit genetic resemblances with schizophrenia, and in addition, we pointed out a potential biomarker and new genes, possibly, involved in SHR fenotype.
Recently, our group demonstrated that Spontaneously Hypertensive Rats (SHR) strain presents a behavioral profile, classically, associated with schizophrenia animal models. The aim of this study was to characterize the expression of neurotransmitter receptors and regulators genes in brain regions (nucleus accumbens – NAcc and prefrontal cortex - CPF) and peripheral blood between SHR (N=8) and Wistar rats (control strain) (N=8), and between SHR animals treated or not with antipsychotic drugs (risperidone – N=8, clozapine – N=7, haloperidol – N=7). We used the PCRarray technology, which verifies the gene expression of 84 genes simultaneously. In the comparison between SHR and Wistar strains we found 4 genes differentially expressed in CPF (Chrnb4, Gad2, Qrfpr e Slc5a7) and one in peripheral blood (Sstr4). We also observed that the gene expression of Tacr3 in peripheral blood of SHR was positively correlated with NAcc and negatively with CPF of SHR animals. Concerning the treatment, we found three genes differentially expressed in CPF of SHR group treated with clozapine (Drd2, Drd3 e Brs3) and two in SHR group treated with haloperidol (Brs3 e Sstr4). In this study, we encountered genes differentially expressed between SHR and Wistar that are involved in important pathways of schizophrenia, such as Gad2 and Tacr3, and the latter, also correlated between blood and brain, suggesting a potential biomarker of SHR condition. In the treatment groups, we found genes probably altered due to the antagonism of D2-like receptors, and genes that can be associated with behavioral improvements after antipsychotic treatment, described previously by our group. In conclusion, our study revealed that SHR strain exhibit genetic resemblances with schizophrenia, and in addition, we pointed out a potential biomarker and new genes, possibly, involved in SHR fenotype.
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Citação
SANTORO, Marcos Leite. Análise da expressão de genes receptores e reguladores de neurotransmissores em um novo modelo animal para esquizofrenia. Tese (Doutorado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2012.