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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Sales, Amanda Juliana [1] ; Lourenco Joca, Samia Regiane [2, 3]
Total Authors: 2
[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
Total Affiliations: 3
Document type: Journal article
Source: ACTA NEUROPSYCHIATRICA; v. 28, n. 1, p. 11-22, FEB 2016.
Web of Science Citations: 16

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)

FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
Grantee:Francisco Silveira Guimaraes
Support type: Research Projects - Thematic Grants
FAPESP's process: 11/17281-7 - Involvement of epigenetic mechanisms induced by DNA methylation on stress-induced behavioral consequences and on the expression of genes involved in the neurobiology of depression
Grantee:Sâmia Regiane Lourenço Joca
Support type: Regular Research Grants