Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA531784 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human postmortem hippocampus: Major depressive disorder (MDD) vs. Control
| PRJNA130293 | ENA
Project description:Homo sapiens Exome sequencing in Major Depressive Disorder
| PRJNA774142 | ENA
Project description:The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are critically implicated in major depressive disorder (MDD), although underlying mechanisms remain enigmatic. Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains and identified ZDHHC21 as a major palmitoyl-transferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression show reduced brain ZDHHC21 expression in conjunction with attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in murine forebrain by itself sufficed to provoke depressive symptoms, demonstrating a causal relationship between 5-HT1AR palmitoylation and depression. Regarding the underlying mechanism, we identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. By analysis of the post-mortem samples from suicide MDD victims we also found ZDHHC21 expression as well as palmitoylation of 5-HT1AR to be specifically reduced within the prefrontal cortex (PFC), a brain area critically involved in the pathogenesis of depressive symptoms. Our study provides evidence for transcriptional downregulation of 5-HT1AR palmitoylation as a central mechanism in the etiology of depression and even suicide, in effect making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of major depressive disorder.
2019-07-16 | PXD012736 | Pride
Project description:Hypermethylation in the ZBTB20 gene is associated with major depressive disorder
| PRJNA235960 | ENA
Project description:Blood transcriptomic markers in patients with late-onset major depressive disorder
| PRJNA308732 | ENA
Project description:Hypermethylation in the ZBTB20 gene is associated with major depressive disorder
| PRJNA236349 | ENA
Project description:DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.
| PRJNA162437 | ENA
Project description:Background: Major Depressive Disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for MDD suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesized that regulatory genomic processes are involved in the pathology of both MDD and suicidality. Methods: Genome-wide patterns of DNA methylation were assessed in depressed MDD suicide completers (n=20) and compared to non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focussed on identifying differentially methylated regions (DMRs) associated with suicidal depression, and epigenetic variation was explored in the context of polygenic risk scores for major depression and MDD suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed MDD suicide completers and polygenic burden for MDD and MDD suicide attempt. Results: We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite-pyrosequencing and replicated in a second set of MDD suicide samples, which is characterized by significant hypomethylation in both cortical brain regions in MDD MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for MDD suicide attempt, but not major depression. MDD suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Conclusions: Our data suggest there are coordinated changes in DNA methylation associated with MDD suicide that may offer novel insights into the molecular pathology associated with depressed MDD suicide completers.
2016-11-01 | GSE88890 | GEO