Journal article
Ethanol-Induced Htr3a Promoter Methylation Changes in Mouse Blood and Brain
Alcoholism, clinical and experimental research, v 37(s1), pp E101-E107
01 Jan 2013
PMID: 22834954
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background Abnormal DNA methylation has been observed in promoter regions of a number of genes in human alcoholics. It is unclear whether DNA methylation changes in alcoholics result directly from alcohol consumption or predated the occurrence of alcohol abuse or dependence and whether altered DNA methylation influences gene expression. Methods We investigated ethanol (EtOH)-induced DNA methylation changes in mouse serotonin receptor 3a gene (Htr3a). A 5-day drinking-in-the-dark paradigm was applied to 28 male outbred CD-1 mice (15 EtOH-drinking and 13 water-drinking). The Sequenom MassARRAY approach was used to quantify methylation levels of 8 CpGs around Htr3a transcription start site in trunk blood and 9 brain regions (dorsomedial prefrontal cortex [DMPFC], ventromedial prefrontal cortex, ventral tegmental area, dorsolateral striatum, dorsomedial striatum [DMSTR], ventral striatum, amygdala, hippocampus [HIPPO], and cerebellum). DNA methylation differences between the 2 groups of mice (EtOH- and water-drinking) were analyzed using multivariate analysis of covariance with consideration of EtOH consumption amount. Expression levels of Htr3a in the DMSTR were measured by real-time PCR in 14 EtOH-drinking and 14 water-drinking male CD-1 mice. Results EtOH drinking increased methylation levels of specific Htr3a promoter CpGs in mouse blood (CpG-27: p = 0.028; CpG+54: p = 0.044) and HIPPO (CpG+151: p = 0.012) but reduced methylation levels of specific Htr3a promoter CpGs in mouse DMSTR (CpG-96: p = 0.020; CpG-27: p = 0.035) and DMPFC (CpG+138: p = 0.011; CpG+151: p = 0.040). Nevertheless, methylation levels of Htr3a promoter CpGs in 6 other brain regions were not significantly altered by EtOH consumption. Additionally, the expression level of Htr3a in the DMSTR was 1.43-fold higher in alcohol-drinking mice than in water-drinking mice (p = 0.044). Conclusions Our findings indicate that alcohol consumption may induce tissue-specific DNA methylation changes and further suggest that Htr3a promoter methylation levels may be reversely correlated with Htr3a expression levels in specific brain regions such as DMSTR.
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Details
- Title
- Ethanol-Induced Htr3a Promoter Methylation Changes in Mouse Blood and Brain
- Creators
- Jacqueline M. Barker - Yale UniversityYuqi Zhang - Florida State UniversityFan Wang - Yale UniversityJane R. Taylor - Yale UniversityHuiping Zhang - Yale University
- Publication Details
- Alcoholism, clinical and experimental research, v 37(s1), pp E101-E107
- Publisher
- Wiley
- Number of pages
- 7
- Grant note
- RL1AA017537 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) K99DA022891 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission K99/R00 DA022891; P50 AA012870; RL AA017537; F31 AA020135 / National Institute of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Alcoholic Beverage Medical Research Foundation (A.B.M.R.F.)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Web of Science ID
- WOS:000313719000013
- Scopus ID
- 2-s2.0-84872500748
- Other Identifier
- 991020099717404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Substance Abuse