Epigenetic Mechanisms of Serotonin Signaling

Holloway, Catherine; González-Maeso, Javier

doi:10.1021/acschemneuro.5b00033

Cited by 42 publications

(25 citation statements)

References 133 publications

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“…However, considering the number of serotonergic receptors and their variations, it is beyond the scope of this paper to review all of them here. For a review of 5-HT receptor-dependent signaling and environmental impact on brain development see: Holloway and Gonzalez-Maeso (2015).…”

Section: Influence Of Genetic and Epigenetic Factorsmentioning

confidence: 99%

Developmental changes in serotonin signaling: Implications for early brain function, behavior and adaptation

et al. 2017

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The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk.

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Section: Influence Of Genetic and Epigenetic Factorsmentioning

confidence: 99%

Developmental changes in serotonin signaling: Implications for early brain function, behavior and adaptation

et al. 2017

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“…This leads to deregulation of histone deacetylase 2 (HDAC2), and subsequent epigenetic variations of glutamate metabotropic receptor 2 gene ( GRM2 ). This may affects response to treatment with GRM2 inhibitors (Holloway & Gonzalez‐Maeso, ).…”

Section: Serotonin Pathway Genes Associated With Szmentioning

confidence: 99%

Genetic variability of serotonin pathway associated with schizophrenia onset, progression, and treatment

Hrovatin

Kunej

Dolžan

2019

American J of Med Genetics Pt B

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Schizophrenia (SZ) onset and treatment outcome have important genetic components, however individual genes do not have strong effects on SZ phenotype. Therefore, it is important to use the pathway-based approach and study metabolic and signaling pathways, such as dopaminergic and serotonergic. Serotonin pathway has an important role in brain signaling, nevertheless, its role in SZ is not as thoroughly examined as that of dopamine pathway. In this study, we reviewed serotonin pathway genes and genetic variations associated with SZ, including variations at DNA, RNA, and epigenetic level.We obtained 30 serotonin pathway genes from Kyoto encyclopedia of genes and genomes and used these genes for the literature review. We extracted 20 protein coding serotonin pathway genes with genetic variations associated with SZ onset, development, and treatment from 31 research papers. Genes associated with SZ are present on all levels of serotonin pathway: serotonin synthesis, transport, receptor binding, intracellular signaling, and reuptake; however, regulatory genes are poorly researched. We summarized common challenges of genetic association studies and presented some solutions. The analysis of reported serotonin pathway-SZ associations revealed lack of information about certain serotonin pathway genes potentially associated with SZ. Furthermore, it is becoming clear that interactions among serotonin pathway genes and their regulators may bring further knowledge about their involvement in SZ. K E Y W O R D Sgenetic association studies, genetic variations, pharamcogenetics, schizophrenia, serotonin pathway

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“…Gene annotation revealed that LOC103692976 is involved in the positive regulation of cyclin-dependent protein serine/threonine kinase. DNA methylation plays a role in the control of neurotransmission [58]. The LOC100910540 gene, which is related to methylation, was up and down-regulated in the E vs M and E + L vs E comparisons, respectively.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Profile of Hippocampus in Rats Model of Acute Myocardial Ischemia in Response to Electroacupuncture

Wu¹,

Wang²,

Wang³

et al. 2020

Preprint

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Background: Electroacupuncture (EA) alleviates acute myocardial ischemia (AMI) by regulating some brain areas, including hippocampus. The locus coeruleus (LC) is the main source of norepinephrine (NE) in the brain, including the hippocampus, and regulates cardiovascular function. The aim of the present work was to assess whether LC mediates the positive effects of EA in AMI by altering gene expression levels in the hippocampus. We addressed this in the present study by hippocampus transcriptome profiling in a rat model of AMI following EA treatment. Results: Myocardial injury markers (ischemia-modified albumin, homocysteine and lipoprotein- associated phospholipase A2) in the serum were downregulated in EA (P<0.05) compared to the M group and upregulated in E+L group (P<0.05) compared to E group. RNA sequencing analysis of the hippocampus revealed that the downregulation of 27 genes in M vs S as well as upregulation of 40 genes in M vs S were reversed by EA. These differentially expressed genes, which were validated by quantitative real-time PCR, were enriched in 20 Kyoto Encyclopedia of Genes and Genomes pathways related to glycerolipid, glycerophospholipid, and arachidonic acid metabolism as well asnervous system function (glutamatergic, cholinergic, serotonergic, GABAergic synapses). Conclusions: LC mediates the beneficial effects of EA on AMI-induced injury may be related to the observed transcriptional regulations in the hippocampus. These results provide molecular-level evidence for the therapeutic efficacy of EA in the treatment of AMI.

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Epigenetic Mechanisms of Serotonin Signaling

Cited by 42 publications

References 133 publications

Developmental changes in serotonin signaling: Implications for early brain function, behavior and adaptation

Developmental changes in serotonin signaling: Implications for early brain function, behavior and adaptation

Genetic variability of serotonin pathway associated with schizophrenia onset, progression, and treatment

Transcriptome Profile of Hippocampus in Rats Model of Acute Myocardial Ischemia in Response to Electroacupuncture

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