Effect of antipsychotic drugs on gene expression in the prefrontal cortex and nucleus accumbens in the spontaneously hypertensive rat (SHR)

Effect of antipsychotic drugs on gene expression in the prefrontal cortex and nucleus accumbens in the spontaneously hypertensive rat (SHR)

Author Santoro, Marcos Leite Autor UNIFESP Google Scholar
Ota, Vanessa Kiyomi Autor UNIFESP Google Scholar
Stilhano, Roberta Sessa Autor UNIFESP Google Scholar
Silva, Patricia Natalia Autor UNIFESP Google Scholar
Santos, Camila Mauricio Autor UNIFESP Google Scholar
Diana, Mariana Cepollaro Autor UNIFESP Google Scholar
Gadelha, Ary Autor UNIFESP Google Scholar
Bressan, Rodrigo Affonseca Autor UNIFESP Google Scholar
Melaragno, Maria Isabel Autor UNIFESP Google Scholar
Han, Sang Won Autor UNIFESP Google Scholar
Abilio, Vanessa Costhek Autor UNIFESP Google Scholar
Belangero, Sintia Iole Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Antipsychotic drugs (APDs) are the standard treatment for schizophrenia. the therapeutic effect of these drugs is dependent upon the dopaminergic D2 blockade, but they also modulate other neurotransmitter pathways. the exact mechanisms underlying the clinical response to APDs are not fully understood. in this study, we compared three groups of animals for the expression of 84 neurotransmitter genes in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Each group was treated with a different APD (risperidone, clozapine or haloperidol), and with a non-treated group of spontaneously hypertensive rats (SHRs), which is an animal model for schizophrenia. This study also explored whether or not differential expression was regulated by DNA methylation in the promoter region (PR). in the clozapine group, we found that Chrng was downregulated in the NAcc and six geneswere downregulated in the PFC. in the haloperidol group, Brs3 and Glra1 were downregulated, as was Drd2 in the clozapine group and Drd3, Galr3 and Gabrr1 in the clozapine and haloperidol groups. We also encountered four hypermethylated CG sites in the Glra1 PR, as well as three in the risperidone group and another in the haloperidol group, when compared to non-treated rats. Following the APD treatment, the gene expression results revealed the involvement of genes that had not previously been described, in addition to the activity of established genes. the investigation of the involvement of these novel genes can lead to better understanding about the specific mechanisms of action of the individual APDs studied. (C) 2014 Elsevier B. V. All rights reserved.
Keywords Spontaneously hypertensive rats
Antipsychotic
Gene expression
DNA methylation
Glra1
Brs3
Drd2
Drd3
Galr3
Gabrr1
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2010/08968-6
FAPESP: 2010/13859-1
Date 2014-08-01
Published in Schizophrenia Research. Amsterdam: Elsevier B.V., v. 157, n. 1-3, p. 163-168, 2014.
ISSN 0920-9964 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 163-168
Origin http://dx.doi.org/10.1016/j.schres.2014.05.015
Access rights Closed access
Type Article
Web of Science ID WOS:000341314100026
URI http://repositorio.unifesp.br/handle/11600/38056

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