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Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques
NIAAA, USA.
NIAAA, USA.
NIAAA, USA.
NIAAA, USA.
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2017 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 44, 11769-11774 p.Article in journal (Refereed) Published
Abstract [en]

Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to deter mine whether a gain-of-function nonsynonymous OXTR SNP inter acted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavior al differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.

Place, publisher, year, edition, pages
NATL ACAD SCIENCES , 2017. Vol. 114, no 44, 11769-11774 p.
Keyword [en]
primate; epigenetic; stress; maternal care; oxytocin
National Category
Genetics
Identifiers
URN: urn:nbn:se:liu:diva-143098DOI: 10.1073/pnas.1706206114ISI: 000414127400072PubMedID: 29078292OAI: oai:DiVA.org:liu-143098DiVA: diva2:1159397
Note

Funding Agencies|Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, NIH

Available from: 2017-11-22 Created: 2017-11-22 Last updated: 2017-11-22

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Heilig, Markus
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Center for Social and Affective NeuroscienceFaculty of Medicine and Health SciencesDepartment of Psychiatry
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