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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Effects of DNA methylation inhibitors and conventional antidepressants on mice behaviour and brain DNA methylation levels

Texto completo
Autor(es):
Sales, Amanda Juliana [1] ; Lourenco Joca, Samia Regiane [2, 3]
Número total de Autores: 2
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14040903 Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-14040903 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: ACTA NEUROPSYCHIATRICA; v. 28, n. 1, p. 11-22, FEB 2016.
Citações Web of Science: 16
Resumo

Objective Stress increases DNA methylation and decreases the expression of genes involved in neural plasticity, while treatment with DNA methyltransferase inhibitors (DNMTi) increases gene expression and induces antidepressant-like effects in preclinical models. Therefore, the aim of the present work was to further investigate the potential antidepressant-like effect induced by DNMTi by evaluating the behavioural effects induced by associating DNMTi treatment with conventional antidepressant drugs in mice submitted to the forced swimming test (FST). In addition, brain levels of DNA methylation were also investigated. Methods Mice received systemic injections of 5-aza-2'-deoxycytidine (5-AzaD, 0.1, 0.2 mg/kg), RG108 (0.1, 0.2, 0.4 mg/kg), desipramine (DES, 2.5, 5, 10 mg/kg) or fluoxetine (FLX, 5, 10, 20, 30 mg/kg) and were submitted to the FST or to the open field test (OFT). Additional groups received a combination of subeffective doses of 5-AzaD or RG108 (DNMTi) with subeffective doses of DES or FLX (antidepressants). Results Subeffective doses of RG108 (0.1 mg/kg) or 5-AzaD (0.1mg/kg) in association with subeffective doses of DES (2.5 mg/kg) or FLX (10 mg/kg) induced significant antidepressant-like effects. Effective doses of RG108 (0.2 mg/kg), 5-AzaD (0.2 mg/kg), DES (10 mg/kg) and FLX (20 mg/kg) atenuated stress-induced changes in DNA methylation levels in the hippocampus and prefrontal cortex. None of the treatments induced locomotor effects in the OFT. Conclusion These results suggest that DNMTi potentiate the behavioural effects of antidepressant drugs in the FST and that antidepressants, as well as DNMTi, are able to modulate stress-induced changes in DNA methylation in brain regions closely associated with the neurobiology of depression. (AU)

Processo FAPESP: 12/17626-7 - Mecanismos celulares e moleculares envolvidos no papel de neurotransmissores atípicos em transtornos neuropsiquiátricos
Beneficiário:Francisco Silveira Guimaraes
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 11/17281-7 - Participação de mecanismos epigenéticos induzidos por metilação do DNA sobre o desenvolvimento das conseqüências comportamentais do estresse e sobre a expressão de genes envolvidos na neurobiologia da depressão
Beneficiário:Sâmia Regiane Lourenço Joca
Linha de fomento: Auxílio à Pesquisa - Regular