Dataset Information

Proteomic profiling of postmortem prefrontal cortex tissue of suicide completers

ABSTRACT: A total of 36 postmortem brain samples (23 suicide completers, 13 control sudden death) were collected. We evaluated the proteome profile in the prefrontal cortex (Brodmann area 9, 10) with TMT-based quantification using LC-MS/MS. Several bioinformatics tools were used to elucidate biological mechanisms related to suicide. Subgroup analysis was conducted to find common differentially expressed proteins (DEPs) among various clinically different groups. Among the 9801 proteins identified in our dataset, 295 proteins were differentially expressed between suicide completers and sudden death subjects. Various bioinformatics analysis revealed that suicide completion is predominately enriched in synaptic functions and synaptogenesis especially in endocannabinoid and GABA signaling pathway. Our finding presents the largest protein pools related to suicide completion, and suggests that newly emerging neurotransmitter systems such as endocannabinoid system and synaptogenesis processes may have an impact upon the biological cascade leading to suicide.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Dongyoon Shin

LAB HEAD: Youngsoo Kim

PROVIDER: PXD029845 | Pride | 2022-05-20

REPOSITORIES: Pride

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Proteomic profiling of postmortem prefrontal cortex tissue of suicide completers.

Kim Min Ji MJ Do Misol M Han Dohyun D Son Minsoo M Shin Dongyoon D Yeo Injoon I Yun Young Hyun YH Yoo Seong Ho SH Choi Hyung Jin HJ Shin Daun D Rhee Sang Jin SJ Ahn Yong Min YM Kim Youngsoo Y

Translational psychiatry 20220405 1

Suicide is a leading cause of death worldwide, presenting a serious public health problem. We aimed to investigate the biological basis of suicide completion using proteomics on postmortem brain tissue. Thirty-six postmortem brain samples (23 suicide completers and 13 controls) were collected. We evaluated the proteomic profile in the prefrontal cortex (Broadmann area 9, 10) using tandem mass tag-based quantification with liquid chromatography-tandem mass spectrometry. Bioinformatics tools were ...[more]

PMID: 35383147

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Project description:Brain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group). DeSeq2 identified 35 genes differentially expressed between groups and surviving adjustment for false discovery rate (adjusted P<0.1). In depression, altered genes include humanin-like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene ontology (GO) analyses revealed lower expression of immune-related pathways such as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and angiogenesis and vascular development in (adjusted P<0.1). Hypothesis-driven GO analysis suggests lower expression of genes involved in oligodendrocyte differentiation, regulation of glutamatergic neurotransmission, and oxytocin receptor expression in both suicide and depression, and provisional evidence for altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis identified differential exon usage in ATPase, class II, type 9B (adjusted P<0.1) in depression. Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorder

Dataset Information

Proteomic profiling of postmortem prefrontal cortex tissue of suicide completers

Publications

Proteomic profiling of postmortem prefrontal cortex tissue of suicide completers.

Similar Datasets

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