ArticleNature communications2019
Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 137 citations in OpenAlex.
- MicroRNAs and suicidality: a systematic review and bioinformatic evaluation.Frontiers in psychiatry · 2026Pooled it
- Pooled it
- Identification and validation of palmitoylation-associated biomarkers in major depressive disorder.Scientific reports · 2026Article
- Bridging molecules and connectome: network biomarkers guided by neurotransmitter architecture in major depressive disorder.Translational psychiatry · 2026Article
- ZDHHC5 and ZDHHC14 promote depression via the mediation of double-negative T cells.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Review
- Epigenetics and immunology: Under-recognized aspects of suicidality.World journal of psychiatry · 2025Review
- From stress to anhedonia: differential gene expression, behavioural and biochemical modulations in resilient versus susceptible mice in an ultrasound model of juvenile depression.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- The DRN-VLO pathway via distinct 5-HT synaptic mechanisms modulates neuropathic pain-induced depressive-like behaviors in mice.The journal of headache and pain · 2025Article
- The molecular mechanisms through which psilocybin prevents suicide: evidence from network pharmacology and molecular docking analyses.Translational psychiatry · 2025Article
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- Review
- MicroRNA signatures in neuroplasticity, neuroinflammation and neurotransmission in association with depression.Journal of physiology and biochemistry · 2025Review
- Article
- Stress resilience is an active and multifactorial process manifested by structural, functional, and molecular changes in synapses.Neurobiology of stress · 2024Article
- The interplay of serotonin 5-HT1A and 5-HT7 receptors in chronic stress.Journal of cell science · 2024Article
- Regulation of neuronal plasticity associated with neuropsychiatric disorders by the orexinergic system.Heliyon · 2024Review
- The regulation of methylation on the Z chromosome and the identification of multiple novel Male Hyper-Methylated regions in the chicken.PLoS genetics · 2024Article
Corrections and comments
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Authors and funding
28 authors at 9 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.