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

Authors
Kim, Hyun JungYoo, HyeijungKim, Ji YeonYang, Soo HyunLee, Hyun WooLee, Heon-JeongSon, Gi HoonKim, Hyun
Issue Date
5월-2022
Publisher
BMC
Keywords
Depression; Gene expression; Habenula; Postmortem; Suicide; Transcriptome
Citation
MOLECULAR BRAIN, v.15, no.1
Indexed
SCIE
SCOPUS
Journal Title
MOLECULAR BRAIN
Volume
15
Number
1
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/143043
DOI
10.1186/s13041-022-00934-7
ISSN
1756-6606
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.
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