RGD Reference Report - Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression. - Rat Genome Database

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

Authors: Melas, PA  Rogdaki, M  Lennartsson, A  Bjork, K  Qi, H  Witasp, A  Werme, M  Wegener, G  Mathe, AA  Svenningsson, P  Lavebratt, C 
Citation: Melas PA, etal., Int J Neuropsychopharmacol. 2012 Jun;15(5):669-79. doi: 10.1017/S1461145711000940. Epub 2011 Jun 20.
RGD ID: 9588311
Pubmed: (View Article at PubMed) PMID:21682946
DOI: Full-text: DOI:10.1017/S1461145711000940

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.


Disease Annotations    
Hyperalgesia  (IMP,ISO)
mental depression  (IDA,IEP,ISO)

Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Dnmt1  (DNA methyltransferase 1)
Dnmt3a  (DNA methyltransferase 3 alpha)
S100a10  (S100 calcium binding protein A10)

Genes (Mus musculus)
Dnmt1  (DNA methyltransferase (cytosine-5) 1)
S100a10  (S100 calcium binding protein A10 (calpactin))

Genes (Homo sapiens)
DNMT1  (DNA methyltransferase 1)
S100A10  (S100 calcium binding protein A10)

Additional Information