Attenuated Palmitoylation of Serotonin Receptor 5-HT1A Affects Receptor Function and Contributes to Depression-Like Behaviors
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine(2019)SCI 4区
Cellular Neurophysiology | Behavioural Neurogenomics | Cell Biophysics | Neuroscience and Brain Technologies | Anatomy & Developmental Biology | Neuro and Sensory Physiology | Sechenov First Moscow State Medical University | Institute of Biology | Institute of Molecular and Translational Therapeutic Strategies | Department of Psychiatry
Abstract
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.
MoreTranslated text
Key words
Depression,G protein-coupled receptors,Science,Humanities and Social Sciences,multidisciplinary
PDF
View via Publisher
AI Read Science
Must-Reading Tree
Example
Generate MRT to find the research sequence of this paper
Data Disclaimer
The page data are from open Internet sources, cooperative publishers and automatic analysis results through AI technology. We do not make any commitments and guarantees for the validity, accuracy, correctness, reliability, completeness and timeliness of the page data. If you have any questions, please contact us by email: report@aminer.cn
Chat Paper
去 AI 文献库 对话