Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm
J Psychiatry Neurosci
; 44(3): 164-176, 2019 05 01.
Article
em En
| MEDLINE
| ID: mdl-30807072
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Processamento Alternativo
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Metilação de DNA
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MicroRNAs
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Receptor 5-HT1A de Serotonina
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Epigênese Genética
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Transtorno Depressivo Maior
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article