Postmortem gene expression profiles in the habenulae of suicides: implication of endothelial dysfunction in the neurovascular system

Hyun Jung Kim, Hyeijung Yoo, Ji Yeon Kim, Soo Hyun Yang, Hyun Woo Lee, Heon Jeong Lee, Gi Hoon Son, Hyun Kim

Research output: Contribution to journalArticlepeer-review

Abstract

The habenula (Hb) is an epithalamic structure that links multiple forebrain areas with the mid/hindbrain monoaminergic systems. As an anti-reward center, it has been implicated in the etiology of various neuropsychiatric disorders, particularly those associated with dysregulated reward circuitry. In this regard, Hb has been proposed as a therapeutic target for treatment-resistant depression associated with a higher risk of suicide. Therefore, we aimed to gain insight into the molecular signatures of the Hb in association with suicide in individuals with major depression. Postmortem gene expression analysis identified 251 differentially expressed genes (DEGs) in the Hb tissue of suicides in comparison with Hb tissues from neurotypical individuals. Subsequent bioinformatic analyses using single-cell transcriptome data from the mouse Hb showed that the levels of a subset of endothelial cell-enriched genes encoding cell–cell junctional complex and plasma membrane-associated proteins, as well as the levels of their putative upstream transcriptional regulators, were significantly affected in suicides. Although our findings are based on a limited number of samples, the present study suggests a potential association of endothelial dysfunction in the Hb with depression and suicidal behavior.

Original languageEnglish
Article number48
JournalMolecular brain
Volume15
Issue number1
DOIs
Publication statusPublished - 2022 Dec

Keywords

  • Depression
  • Gene expression
  • Habenula
  • Postmortem
  • Suicide
  • Transcriptome

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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