Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression
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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.
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In the PFC, reduced p11 is associated with increased repressive methylation on the p11 promotor.
“In the PFC, reduced p11 is associated with increased repressive methylation on the p11 promotor [164], but it is unclear if this also occurs in NAc ChIs.”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [164]
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- Authors
- Melas, P. A., Rogdaki, M., Lennartsson, A., Björk, K., Qi, H., Witasp, A., Werme, M., Wegener, G., Mathé, A. A., Svenningsson, P., & Lavebratt, C.
- Affiliations
- Karolinska Institutet (SE)
- Aarhus University Hospital (DK)
- Corresponding author
- Melas, Philippe A.
- ORCID
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-06-20
- Volume
- 15
- Issue
- 05
- Pages
- 669-679
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2135909729
- Cited by
- 157
- References
- 43
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 3 · 2022: 10 · 2021: 10 · 2020: 7 · 2019: 28 · 2018: 9 · 2017: 9 · 2016: 13 · 2015: 16 · 2014: 16 · 2013: 14 · 2012: 14
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd (271-08-0768)
- Bodossaki Foundation
- Karolinska Institutet
- Vetenskapsrådet (10414)
- Medical Research Council
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- p11, S100A10, depression, antidepressant treatment, DNA methylation, epigenetic regulation, Flinders Sensitive Line rats, prefrontal cortex, escitalopram, selective serotonin reuptake inhibitors, DNA methyltransferases, DNMT1, DNMT3A, gene expression
- MeSH terms
- DNA (Cytosine-5-)-Methyltransferase 1, DNA Methyltransferase 3A, S100 Calcium Binding Protein A10, Animals, Depressive Disorder, Disease Models, Animal, DNA (Cytosine-5-)-Methyltransferases, Female, Gene Expression Regulation, S100 Proteins, RNA, Messenger, Citalopram, Annexin A2, Selective Serotonin Reuptake Inhibitors, Prefrontal Cortex, Rats, Epigenomics
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