Effects of DNA methyltransferase inhibitors on the modulation of anxiety-related aversive behaviors

Name: Mayana Cardoso de OliveiraType: MSc dissertationPublication date: 15/12/2017Advisor:

Namesort descending Role
Valquíria Camin de Bortoli Advisor *
Vanessa Beijamini Harres Co-advisor *

Examining board:

Namesort descending Role
Daniela Amorim Melgaço Guimarães do Bem Internal Examiner *
Lívia Carla de Melo Rodrigues External Examiner *
Valquíria Camin de Bortoli Advisor *
Vanessa Beijamini Harres Co advisor *

Summary: Anxiety disorders such as generalized anxiety disorder (GAD) and panic disorder (PT), cause significant impacts on the lives of patients affected by them. Pharmacological treatment of GAD and PT presents problems of efficacy and safety. In this sense, new pharmacological targets have been studied in order to develop more effective treatment options. The pathogenesis of anxiety disorders is complex in nature and interacts with environmental and biological factors, particularly genetic factors. Recently, it has been shown that epigenetic processes can influence gene regulation and mediate adaptation to environmental factors in mental disorders, characterized by a stable hereditary phenotype resulting from changes in the chromosome without changes in the DNA sequence. Epigenetic modifications include changes in DNA, such as methylation, which consists of the addition of a methyl (CH3) catalyzed enzyme by DNA methyltransferases (DNMTs). Thus, the present study tested the hypothesis that the acute systemic treatment with DNA methyltransferase inhibitors, 5-Aza D and RG 108 at doses of 0.2 and 0.4 mg/kg, would have an anxiolytic-like effect and/or antipanic-like effect in animals submitted to the elevated T-maze and anxiolytic-like effect in the light-dark test. Both ethological models of anxiety. Our results show that 5-Aza D in the lowest dose tested reduced of the inhibitory avoidance 1 (E1) in the elevated T-maze, as well as increased time spent in the light compartment in the light-dark test and the number of transitions in the two doses tested compared to the control group, suggesting an anxiolytic-like effect of this drug. RG 108 had no statistically significant effect on elevated T-maze, but increased time spent in the light compartment at the two doses used and the number of transitions between the light and dark compartments at the dose of 0.4 mg/kg in the light-dark test, suggesting an anxiolytic-like effect of this drug in this model. Thus, the results of the present study suggest a possible therapeutic action of DNA methyltransferase inhibitors in anxiety disorders.

Key words: DNA methylation, generalized anxiety, panic, elevated T-maze, light- dark test, DNA methyltransferase inhibitors.Access to document

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