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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

Grant number: 11/17281-7
Support type:Regular Research Grants
Duration: March 01, 2012 - February 28, 2014
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Sâmia Regiane Lourenço Joca
Grantee:Sâmia Regiane Lourenço Joca
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. researchers:Francisco Silveira Guimaraes

Abstract

Recent studies indicate that epigenetic mechanisms migh be involved in the neurobiology of depression. For example, DNA methylation, which is associated with transcriptional repression, is increased by exposure to stress. Besides, high levels of methylation in specific gene loci were found in the brains of suicide victims. In addition, preliminary results of our research group showed that systemic administration of inhibitors of DNA methylation induces antidepressant-like effect in the forced swimming test. However, the molecular mechanisms and brain structures involved in these effects, as well as the pharmacological profile induced by these treatments, have not been investigated yet. Moreover, the effects induced by these treatments in animals exposed to other animal models predictive of antidepressant effects remains to be investigated.Therefore, this project aims to continue the investigation about the involvement of DNA methylation in the development of behavioral consequences induced by stress by studying the effects induced by other inhibitors of DNA methylation, as well as the molecular mechanisms involved in these effects. To do so, it will be tested the effects induced by acute and subchronic administration of nucleoside (5-aza-2-deoxiitidina) and non-nucleoside (RG-108) inhibitors of DNA methylation on the behavior of animals submitted to different models that involve presentation of stress (forced swimming, footshocks, restraint). In addition, we intend to evaluate the pattern of DNA methylation in candidate genes in structures involved in depression patophisyiology (hippocampus, prefrontal cortex and striatum) in response to treatment with DNA methylation inhibitors or with antidepressant drugs, in stressed and non stressed animals. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Study tests new class of drugs with potential antidepressant effects 

Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SALES, AMANDA J.; JOCA, SAMIA R. L. Antidepressant administration modulates stress-induced DNA methylation and DNA methyltransferase expression in rat prefrontal cortex and hippocampus. Behavioural Brain Research, v. 343, p. 8-15, MAY 2 2018. Web of Science Citations: 2.
SALES, AMANDA JULIANA; LOURENCO JOCA, SAMIA REGIANE. Effects of DNA methylation inhibitors and conventional antidepressants on mice behaviour and brain DNA methylation levels. ACTA NEUROPSYCHIATRICA, v. 28, n. 1, p. 11-22, FEB 2016. Web of Science Citations: 16.
PEREIRA, VITOR S.; CASAROTTO, PLINIO C.; HIROAKI-SATO, VINICIUS A.; SARTIM, ARIANDRA G.; GUIMARAES, FRANCISCO S.; JOCA, SAMIA R. L. Antidepressant- and anticompulsive-like effects of purinergic receptor blockade: Involvement of nitric oxide. European Neuropsychopharmacology, v. 23, n. 12, p. 1769-1778, DEC 2013. Web of Science Citations: 25.
SCOPINHO, AMERICA A.; LISBOA, SABRINA F. S.; GUIMARAES, FRANCISCO S.; CORREA, FERNANDO M. A.; RESSTEL, LEONARDO B. M.; JOCA, SAMIA R. L. Dorsal and Ventral Hippocampus Modulate Autonomic Responses but Not Behavioral Consequences Associated to Acute Restraint Stress in Rats. PLoS One, v. 8, n. 10 OCT 17 2013. Web of Science Citations: 13.

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