Antidepressant administration modulates stress-induced DNA methylation and DNA methyltransferase expression in rat prefrontal cortex and hippocampus

Author(s)

Sales, Amanda J. ^[1] ; Joca, Samia R. L. ^{[2, 3, 4]}

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto, SP - Brazil

^[4] Aarhus Univ, Translat Neuropsychiat Unit, Dept Clin Med, Aarhus - Denmark

• Document type: Journal article
• Source: Behavioural Brain Research; v. 343, p. 8-15, MAY 2 2018.
• Web of Science Citations: 2

Abstract

Stress and antidepressant treatment can modulate DNA methylation in promoter region of genes related to neuroplasticity and mood regulation, thus implicating this epigenetic mechanism in depression neurobiology and treatment. Accordingly, systemic administration of DNA methyltransferase (DNMT) inhibitors induces antidepressant-like effects in rodents. DNA methylation is conveyed by DNMT 1, 3a and 3b isoforms, which are differentially expressed in the brain. In order to investigate if the behavioral effects of antidepressants could be associated with changes in DNA methylation and DNMT expression, we investigated the effects induced by acute and repeated antidepressant treatment on DNA methylation and DNMT expression (1, 3a and 3b isoforms) in different brain regions of rats exposed to a stress model of depression, the learned helplessness (LH). Therefore, rats were exposed to pretest and treated with one or seven injections of vehicle or imipramine (15 mg kg(-1)), with test session performed one hour after the last injection. Chronic, but not acute, imipramine administration attenuated escape failures during the test, a well described antidepressant-like effect in this model. DNA methylation and DNMT (1, 3a and 3b) levels were measured in the dorsal and ventral hippocampus vHPC) and in the prefrontal cortex (PFC) of rats exposed to stress and treatment. Stress increased DNA methylation, DNMT3a and DNMT3b expression in the dHPC and PFC. Chronic, but not acute, imipramine administration attenuated stress effects only in the PFC. These results suggest the regulation of DNA methylation in the PFC may be an important mechanism for antidepressant-like effects in the LH model. (AU)

• 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