HDAC2를 매개로 하는 TRPV1의 스트레스 반응 조절 기전
- Title
- HDAC2를 매개로 하는 TRPV1의 스트레스 반응 조절 기전
- Other Titles
- TRPV1 regulates stress responses through HDAC2
- Author
- 왕성은
- Advisor(s)
- 손현
- Issue Date
- 2017-08
- Publisher
- 한양대학교
- Degree
- Doctor
- Abstract
- Transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel mainly involved in pain sensation, affects mood and neuroplasticity in the brain, where its role is still poorly understood. Here I show that Trpv1-deficient (Trpv1-/-) mice have an antidepressant-like phenotype following chronic unpredictable stress and basal hippocampal neurogenesis is enhanced. I also found that glucocorticoid receptor (GR)-mediated histone deacetylase (HDAC) 2 expression and activity are reduced in the Trpv1-/- mice. At the same time, levels of p16 and p21, which are implicated in the cell-cycle, are reduced, while levels of neuroplasticity-related molecules are elevated through HDAC2. Hippocampal knockdown of TRPV1 had similar effects both at the behavioral and molecular levels and its antidepressant-like behavioral effects are blocked by HDAC2 overexpression. Furthermore, I found that capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide) treatment resulted in upregulation of HDAC2 in the mouse hippocampus, and HDAC2 was enriched at the promoters of synaptic plasticity-related genes. Collectively, these findings define a novel pathway involving an important role for TRPV1 in chromatin regulation in the adult brain. This pathway provides a molecular link between TRPV1 activity and depression.
- URI
- http://hdl.handle.net/20.500.11754/33834http://hanyang.dcollection.net/common/orgView/200000430968
- Appears in Collections:
- GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > BIOMEDICAL SCIENCE(의생명과학과) > Theses (Master)
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