Epigenetic regulation in psychiatric disorders

Tsankova, Nadia M.; Renthal, William; Kumar, Arvind; Nestler, Eric J.

doi:10.1038/nrn2132

Cited by 1,214 publications

(542 citation statements)

References 101 publications

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“…Epigenetic regulation, including DNA methylation and histone modification, is essential for normal brain development, and dysregulation of the epigenetic machinery has been implicated in various neurodevelopmental and neuropsychiatric disorders, including ASD 4. microRNA (miRNA) is a well‐known epigenetic component that post‐transcriptionally regulates gene expression by binding to complementary nucleotide sequences in the 3′ untranslated region of target mRNAs 5.…”

Section: Introductionmentioning

confidence: 99%

Maternal immune activation alters brain microRNA expression in mouse offspring

Sunwoo

Jeon²,

Moon

et al. 2018

Ann Clin Transl Neurol

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ObjectiveMaternal immune activation (MIA) is associated with an increased risk of autism spectrum disorder (ASD) in offspring. Herein, we investigate the altered expression of microRNAs (miRNA), and that of their target genes, in the brains of MIA mouse offspring.MethodsTo generate MIA model mice, pregnant mice were injected with polyriboinosinic:polyribocytidylic acid on embryonic day 12.5. We performed miRNA microarray and mRNA sequencing in order to determine the differential expression of miRNA and mRNA between MIA mice and controls, at 3 weeks of age. We further identified predicted target genes of dysregulated miRNAs, and miRNA‐target interactions, based on the inverse correlation of their expression levels.ResultsMice prenatally subjected to MIA exhibited behavioral abnormalities typical of ASD, such as a lack of preference for social novelty and reduced prepulse inhibition. We found 29 differentially expressed miRNAs (8 upregulated and 21 downregulated) and 758 differentially expressed mRNAs (542 upregulated and 216 downregulated) in MIA offspring compared to controls. Based on expression levels of the predicted target genes, 18 downregulated miRNAs (340 target genes) and three upregulated miRNAs (60 target genes) were found to be significantly enriched among the differentially expressed genes. miRNA and target gene interactions were most significant between mmu‐miR‐466i‐3p and Hfm1 (ATP‐dependent DNA helicase homolog), and between mmu‐miR‐877‐3p and Aqp6 (aquaporin 6).InterpretationOur results provide novel information regarding miRNA expression changes and their putative targets in the early postnatal period of brain development. Further studies will be needed to evaluate potential pathogenic roles of the dysregulated miRNAs.

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Section: Introductionmentioning

confidence: 99%

Maternal immune activation alters brain microRNA expression in mouse offspring

Sunwoo

Jeon²,

Moon

et al. 2018

Ann Clin Transl Neurol

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show abstract

“…Studies of epigenetic mechanisms make it possible, for the first time, to push the envelope one step further and directly examine transcriptional regulation in the brains of behaving animals ( Tsankova et al 2007). Historically, the term epigenetics describes mechanisms by which cellular traits can be inherited without a change in DNA sequence.…”

Section: Epigenetic Mechanisms Of Dfosb Actionmentioning

confidence: 99%

Transcriptional mechanisms of addiction: role of ΔFosB

Nestler

2008

Phil. Trans. R. Soc. B

347

381

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Regulation of gene expression is considered a plausible mechanism of drug addiction, given the stability of behavioural abnormalities that define an addicted state. Among many transcription factors known to influence the addiction process, one of the best characterized is DFosB, which is induced in the brain's reward regions by chronic exposure to virtually all drugs of abuse and mediates sensitized responses to drug exposure. Since DFosB is a highly stable protein, it represents a mechanism by which drugs produce lasting changes in gene expression long after the cessation of drug use. Studies are underway to explore the detailed molecular mechanisms by which DFosB regulates target genes and produces its behavioural effects. We are approaching this question using DNA expression arrays coupled with the analysis of chromatin remodelling-changes in the posttranslational modifications of histones at drug-regulated gene promoters-to identify genes that are regulated by drugs of abuse via the induction of DFosB and to gain insight into the detailed molecular mechanisms involved. Our findings establish chromatin remodelling as an important regulatory mechanism underlying drug-induced behavioural plasticity, and promise to reveal fundamentally new insight into how DFosB contributes to addiction by regulating the expression of specific target genes in brain reward pathways.

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“…45 In addition to genetic variations, epigenetic modifications contribute to psychiatric pathologies such as depression, bipolar disorder and schizophrenia. 3,5,6,46,47 In the brains of suicide victims that suffered from major depressive disorder, gene-specific aberrations in DNA methylation were apparent in the gammaaminobutyric acid receptor alpha1 (GABRA1) subunit promoter region and the GABRA1 transcript was under-expressed within the frontopolar cortex. 48,49 Decreased levels of glucocorticoid receptor (NR3C1) mRNA, as well as increased methylation of the promoter, were observed in the hippocampus obtained from suicide victims with a history of childhood abuse.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5][6] Epigenetic regulation is mediated through altered chromatin structure, which is correlated with changes in DNA methylation and histone modifications. Gene promoters are often located in GC-and CpG-rich DNA regions, so called CpG islands.…”

Section: Introductionmentioning

confidence: 99%