Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression

被引:105
作者
Melas, Philippe A. [1 ]
Rogdaki, Maria
Lennartsson, Andreas [2 ]
Bjork, Karl [3 ]
Qi, Hongshi [3 ]
Witasp, Anna
Werme, Martin [4 ]
Wegener, Gregers [5 ]
Mathe, Aleksander A. [4 ]
Svenningsson, Per [3 ]
Lavebratt, Catharina
机构
[1] Karolinska Inst, Dept Mol Med & Surg, Neurogenet Unit, Karolinska Univ Hosp,CMM L8 00, S-17176 Stockholm, Sweden
[2] Karolinska Inst, Ctr Biosci, Dept Biosci & Nutr, S-17176 Stockholm, Sweden
[3] Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, S-17176 Stockholm, Sweden
[4] Karolinska Inst, Sect Psychiat, Dept Clin Neurosci, S-17176 Stockholm, Sweden
[5] Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark
基金
瑞典研究理事会; 英国医学研究理事会;
关键词
Depression; DNA methylation; epigenetics; escitalopram; P11 (S100A10); DNA METHYLTRANSFERASES DNMT3A; METHYLATION CHANGES; MESSENGER-RNA; RAT MODEL; EXPRESSION; DEMETHYLATION; CELLS; CITALOPRAM; FOREBRAIN; ELEMENTS;
D O I
10.1017/S1461145711000940
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
P11 (S100A10) has been associated with the pathophysiology of depression both in human and rodent models. Different types of antidepressants have been shown to increase P11 levels in distinct brain regions and P11 gene therapy was recently proven effective in reversing depressive-like behaviours in mice. However, the molecular mechanisms that govern P11 gene expression in response to antidepressants still remain elusive. In this study we report decreased levels of P11, associated with higher DNA methylation in the promoter region, in the prefrontal cortex of the Flinders Sensitive Line (FSL) genetic rodent model of depression. This hypermethylated pattern was reversed to normal, as indicated by the control line, after chronic administration of escitalopram (a selective serotonin reuptake inhibitor; SSRI). The escitalopram-induced hypomethylation was associated with both an increase in P11 gene expression and a reduction in mRNA levels of two DNA methyltransferases that have been shown to maintain DNA methylation in adult forebrain neurons (Dnmt1 and Dnmt3a). In conclusion, our data further support a role for P11 in depression-like states and suggest that this gene is controlled by epigenetic mechanisms that can be affected by antidepressant treatment.
引用
收藏
页码:669 / 679
页数:11
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