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Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain.
- Source :
-
American Journal of Physiology: Regulatory, Integrative & Comparative Physiology . Sep2015, Vol. 309 Issue 5, pR613-R622. 10p. - Publication Year :
- 2015
-
Abstract
- Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitaryadrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03636119
- Volume :
- 309
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Regulatory, Integrative & Comparative Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 109330820
- Full Text :
- https://doi.org/10.1152/ajpregu.00075.2015