Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm
Journal
Journal of psychiatry & neuroscience : JPN
ISSN: 1488-2434
Titre abrégé: J Psychiatry Neurosci
Pays: Canada
ID NLM: 9107859
Informations de publication
Date de publication:
01 05 2019
01 05 2019
Historique:
entrez:
27
2
2019
pubmed:
27
2
2019
medline:
10
6
2020
Statut:
ppublish
Résumé
Major depression and anxiety are highly prevalent and involve chronic dysregulation of serotonin, but they remain poorly understood. Here, we review novel transcriptional (genetic, epigenetic) and posttranscriptional (microRNA, alternative splicing) mechanisms implicated in mental illness, focusing on a key serotonin-related regulator, the serotonin 1A (5-HT1A) receptor. Functional single-nucleotide polymorphisms and stress-induced DNA methylation of the 5-HT1A promoter converge to differentially alter pre- and postsynaptic 5-HT1A receptor expression associated with major depression and reduced therapeutic response to serotonergic antidepressants. Major depression is also associated with altered levels of splice factors and microRNA, posttranscriptional mechanisms that regulate RNA stability. The human 5-HT1A 3′-untranslated region is alternatively spliced, removing microRNA sites and increasing 5-HT1A expression, which is reduced in major depression and may be genotype-dependent. Thus, the 5-HT1A receptor gene illustrates the convergence of genetic, epigenetic and posttranscriptional mechanisms in gene expression, neurodevelopment and neuroplasticity, and major depression. Understanding gene regulatory mechanisms could enhance the detection, categorization and personalized treatment of major depression.
Identifiants
pubmed: 30807072
doi: 10.1503/jpn.180209
pmc: PMC6488484
Substances chimiques
MicroRNAs
0
Receptor, Serotonin, 5-HT1A
112692-38-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
164-176Informations de copyright
© 2019 Joule Inc. or its licensors
Déclaration de conflit d'intérêts
P. Albert sits on the JPN editorial board. He was not involved in the decision-making on this manuscript. No other competing interests declared.
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