Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Gene Expression Profiling of the Habenula in Rats Exposed to Chronic Restraint Stress

  • Yoo, Hyeijung (Department of Anatomy, College of Medicine, Korea University) ;
  • Kim, Hyun Jung (Department of Anatomy, College of Medicine, Korea University) ;
  • Yang, Soo Hyun (Department of Anatomy, College of Medicine, Korea University) ;
  • Son, Gi Hoon (Department of Legal Medicine, College of Medicine, Korea University) ;
  • Gim, Jeong-An (Medical Science Research Center, College of Medicine, Korea University) ;
  • Lee, Hyun Woo (Department of Anatomy, College of Medicine, Korea University) ;
  • Kim, Hyun (Department of Anatomy, College of Medicine, Korea University)
  • Received : 2021.10.21
  • Accepted : 2022.02.07
  • Published : 2022.05.31
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Abstract

Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress. These genes were enriched in neuroactive ligand-receptor interaction, the cAMP (cyclic adenosine monophosphate) signaling pathway, circadian entrainment, and synaptic signaling from the Kyoto Encyclopedia of Genes and Genomes pathway analysis and responded to corticosteroids, positive regulation of lipid transport, anterograde trans-synaptic signaling, and chemical synapse transmission from the Gene Ontology analysis. Based on protein-protein interaction network analysis of the DEGs, we identified neuroactive ligand-receptor interactions, circadian entrainment, and cholinergic synapse-related subclusters. Additionally, cell type and habenular regional expression of DEGs, evaluated using a recently published single-cell RNA sequencing study (GSE137478), strongly suggest that DEGs related to neuroactive ligand-receptor interaction and trans-synaptic signaling are highly enriched in medial habenular neurons. Taken together, our findings provide a valuable set of molecular targets that may play important roles in mediating the habenular response to stress and the onset of chronic stress-induced depressive behaviors.

Keywords

Acknowledgement

This research was supported by the Ministry of Science and ICT through the National Research Foundation of Korea (NRF-2017M3C7A1079692 to H.K., NRF-2017R1D1A1B06032730 to H.W.L., and NRF-2019M3C7A1032764 to G.H.S.).

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