DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression

BMC Psychiatry

Research Article

Martin Alda¹  Corina Nagy²  Juan Pablo Lopez²  Elizabeth S. Chen²  David R. Checknita²  Gustavo Turecki³  Elena Kutsarova⁴  Cristiana Cruceanu⁴  Guy A. Rouleau⁵ 

[1] Department of Psychiatry, Dalhousie University, Halifax, NS, Canada;McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada;McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada;Douglas Mental Health Institute, McGill University, 6875 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada;McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada;Montreal Neurological Institute, McGill University, Montreal, QC, Canada;Montreal Neurological Institute, McGill University, Montreal, QC, Canada;

关键词: Bipolar disorder;    Major depressive disorder;    DNA Methylation;    Epigenetics;    Mood disorders;   

DOI  :  10.1186/s12888-016-0989-0

 received in 2015-11-26, accepted in 2016-08-02,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe Synapsins (SYN1, SYN2, and SYN3) are important players in the adult brain, given their involvement in synaptic transmission and plasticity, as well as in the developing brain through roles in axon outgrowth and synaptogenesis. We and others previously reported gene expression dysregulation, both as increases and decreases, of Synapsins in mood disorders, but little is known about the regulatory mechanisms leading to these differences. Thus, we proposed to study DNA methylation at theses genes’ promoter regions, under the assumption that altered epigenetic marks at key regulatory sites would be the cause of gene expression changes and thus part of the mood disorder etiology.MethodsWe performed CpG methylation mapping focusing on the three genes’ predicted CpG islands using the Sequenom EpiTYPER platform. DNA extracted from post-mortem brain tissue (BA10) from individuals who had lived with bipolar disorder (BD), major depressive disorder (MDD), as well as psychiatrically healthy individuals was used. Differences in methylation across all CpGs within a CpG island and between the three diagnostic groups were assessed by 2-way mixed model analyses of variance.ResultsWe found no significant results for SYN1 or SYN3, but there was a significant group difference in SYN2 methylation, as well as an overall pattern of hypomethylation across the CpG island. Furthermore, we found a significant inverse correlation of DNA methylation with SYN2a mRNA expression.ConclusionsThese findings contribute to previous work showing dysregulation of Synapsins, particularly SYN2, in mood disorders and improve our understanding of the regulatory mechanisms that precipitate these changes likely leading to the BD or MDD phenotype.

【 授权许可】

CC BY   
© The Author(s). 2016