In search of the Molecular Basis of Major Depression and Antidepressants

Yong-Seok Oh
Yong-Seok Oh
DGIST, Korea
13:55~14:40, November 21st, 2014

Abstract :

Major depressive disorder (MDD) is a chronic, recurrent, and even life-threatening mental disease, which affects up to 20 % of the population worldwide. Despite intense research over several decades, our understanding of the pathophysiology of this disease, as well as the anti-depressive mechanism of current therapeutics, has remained unclear. Our previous studies revealed the profound roles of p11 (S100A10) protein and its protein complex, in mood regulation and antidepressant actions. We show that SMARCA3, a chromatin-remodeling factor, is a molecular target for the p11-dependent antidepressant actions. Formation of heterohexameric complex with p11/Annexin A2 increases the DNA-binding affinity of SMARCA3 and its localization to the nuclear matrix fraction. In the dentate gyrus, both p11 and SMARCA3 are highly enriched in hilar mossy cells and basket cells. The SSRI fluoxetine induces expression of p11 in both cell types and increases the amount of the ternary complex of p11/annexin A2/SMARCA3. SSRI-induced neurogenesis and behavioral responses are abolished by constitutive knockout of SMARCA3. Our studies indicate a central role for a chromatin-remodeling factor in the SSRI/p11 signaling pathway. Our current projects further aim to decoding the cell type-specific transcriptional mechanism for the antidepressant actions of p11/Annexin A2/SMARCA3 complex. This study will suggest a novel approach to the development of improved antidepressant therapies.


Research Interests

Monoaminergic regulation of the CNS and mood/anxiety disorder


Awards and Honors

  • 2014 : Principal Investigator, HRHR (High-Risk High-Reward) Project from DGIST (2014-2015)
  • 2014 : Principal Investigator, New Investigator Support Program from Korea Research Foundation (2014-2017)
  • 2013 : Principal Investigator, The NARSAD* Young Investigator Award from Brain & Behavior Research Foundation (2014-2016)
  • 2013 : Selected Participant, Cold Spring Harbor Workshop Course on Advanced/Next-Generation Sequencing Technologies and its Applications
  • 2013 : Recipient, The Travel Grant Award from The Korean Society for Molecular and Cellular Biology
  • 2006 : Recipient, Korean Oversea Post-doctoral Fellowship from Korea Research Foundation
  • 1993-1997 : Recipient, Superior Academic Performance Scholarship from Seoul National University