期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-11876-5
关键词
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资金
- Deutsche Forschungsgemeinschaft (DFG) [PO732]
- Russian Scientific Foundation [19-15-00025]
- 5-100 Russian Academic Excellence Project
- NARSAD
- Brain and Behavior Research Fund, Young Investigator Award
- Consolidator ERC grant from the European Union
- REBIRTH Excellence cluster
- National Science Centre [UMO-2017/26/E/NZ4/00637]
- Polish Ministry of Science [1342/1/MOB/IV/15/2016/0]
- [0324-2019-0041]
- Russian Science Foundation [19-15-00025] Funding Source: Russian Science Foundation
The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD.
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