We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques.
- Authors
Kinnally, E. L.; Capitanio, J. P.; Leibel, R.; Deng, L.; LeDuc, C.; Haghighi, F.; Mann, J. J.
- Abstract
Epigenetic mechanisms may moderate genetic and environmental risk ( G× E) for mood disorders. We used an experimental rhesus macaque model of early life stress to test whether epigenetic regulation of serotonin transporter ( 5-HTT) may contribute to G× E interactions that influence behavior and emotion. We hypothesized that peripheral blood mononuclear cell (PBMC) DNA methylation within an 800 bp cytosine–phosphate–guanosine (CpG) island that overlaps with the 5-HTT transcription initiation start site, a hypothesized model of the same genomic region in brain tissue, would mediate or moderate the effects of early life stress and a functional 5-HTT promoter polymorphism ( rh5-HTTLPR) on two outcomes: PBMC 5-HTT expression and behavioral stress reactivity. Eighty-seven infant rhesus macaques (3–4 months of age) were either mother reared in large social groups ( n = 70) or nursery reared ( n = 17). During a maternal/social separation, infants' blood was sampled and behavioral stress reactivity recorded. PBMC DNA and RNA samples were used to determine rh5-HTTLPR genotype, 5-HTT mRNA expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and 5-HTT CpG methylation status using sodium bisulfite pyrosequencing. Consistent with human data, carriers of the low-expressing rh5-HTTLPR alleles exhibited higher mean 5-HTT CpG methylation, which was associated with lower PBMC 5-HTT expression. Higher 5-HTT CpG methylation, but not rh5-HTTLPR genotype, exacerbated the effects of early life stress on behavioral stress reactivity in infants. 5-HTT CpG methylation may be an important regulator of 5 -HTT expression early in development and may contribute to the risk for mood disorders observed in ‘high-risk’ 5-HTTLPR carriers.
- Subjects
SEROTONIN; GENE expression; AFFECTIVE disorders; RHESUS monkeys; GENOTYPE-environment interaction; METHYLATION
- Publication
Genes, Brain & Behavior, 2010, Vol 9, Issue 6, p575
- ISSN
1601-1848
- Publication type
Article
- DOI
10.1111/j.1601-183X.2010.00588.x