Antidepressant treatment is associated with epigenetic alterations of Homer1 promoter in a mouse model of chronic depression.

Lu Sun, Rikst-Nynke Verkaik-Schakel, Knut Biber, Torsten Plösch, Tsvetan Serchov

Journal of affective disorders 2021 Jan 15

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Understanding the neurobiology of depression and the mechanism of action of therapeutic measures is currently a research priority. We have shown that the expression of the synaptic protein Homer1a correlates with depression-like behavior and its induction is a common mechanism of action of different antidepressant treatments. However, the mechanism of Homer1a regulation is still unknown. We combined the chronic despair mouse model (CDM) of chronic depression with different antidepressant treatments. Depression-like behavior was characterized by forced swim and tail suspension tests, and via automatic measurement of sucrose preference in IntelliCage. The Homer1 mRNA expression and promoter DNA methylation were analyzed in cortex and peripheral blood by qRT-PCR and pyrosequencing. CDM mice show decreased Homer1a and Homer1b/c mRNA expression in cortex and blood samples, while chronic treatment with imipramine and fluoxetine or acute ketamine application increases their level only in the cortex. The quantitative analyses of the methylation of 7 CpG sites, located on the Homer1 promoter region containing several CRE binding sites, show a significant increase in DNA methylation in the cortex of CDM mice. In contrast, antidepressant treatments reduce the methylation level. Homer1 expression and promotor methylation were not analyzed in different blood cell types. Other CpG sites of Homer1 promoter should be investigated in future studies. Our experimental approach does not distinguish between methylation and hydroxymethylation. We demonstrate that stress-induced depression-like behavior and antidepressant treatments are associated with epigenetic alterations of Homer1 promoter, providing new insights into the mechanism of antidepressant treatment. Copyright © 2020. Published by Elsevier B.V.

Citation

Lu Sun, Rikst-Nynke Verkaik-Schakel, Knut Biber, Torsten Plösch, Tsvetan Serchov. Antidepressant treatment is associated with epigenetic alterations of Homer1 promoter in a mouse model of chronic depression. Journal of affective disorders. 2021 Jan 15;279:501-509