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Early rearing histo...
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Baker, MaggieNIAAA, USA
(author)
Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017-10-16
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NATL ACAD SCIENCES,2017
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printrdacarrier
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LIBRIS-ID:oai:DiVA.org:liu-143098
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-143098URI
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https://doi.org/10.1073/pnas.1706206114DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Funding Agencies|Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, NIH
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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.
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Lindell, Stephen G.NIAAA, USA
(author)
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Driscoll, Carlos A.NIAAA, USA
(author)
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Zhou, ZhifengNIAAA, USA
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Yuan, QiaopingNIAAA, USA
(author)
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Schwandt, Melanie L.NIAAA, USA
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Miller-Crews, IsaacNIAAA, USA
(author)
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Simpson, Elizabeth A.Eunice Shriver Kennedy National Institute Child Health and Huma, MD 20837 USA
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Paukner, AnnikaEunice Shriver Kennedy National Institute Child Health and Huma, MD 20837 USA
(author)
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Francesco Ferrari, PierUniversity of Claude Bernard Lyon, France
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Kumar Sindhu, RaviNIAAA, MD 20852 USA
(author)
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Razaqyar, MuslimaNIAAA, USA
(author)
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Sommer, Wolfgang H.Heidelberg University, Germany; Heidelberg University, Germany
(author)
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Lopez, Juan F.University of Michigan, MI 48109 USA
(author)
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Thompson, Robert C.University of Michigan, MI 48109 USA
(author)
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Goldman, DavidNIAAA, USA
(author)
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Heilig, MarkusLinköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten,Region Östergötland, Psykiatriska kliniken(Swepub:liu)marhe41
(author)
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Dee Higley, J.Brigham Young University, UT 84602 USA
(author)
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Suomi, Stephen J.Eunice Shriver Kennedy National Institute Child Health and Huma, MD 20837 USA
(author)
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Barr, Christina S.NIAAA, USA
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NIAAA, USAEunice Shriver Kennedy National Institute Child Health and Huma, MD 20837 USA
(creator_code:org_t)
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In:Proceedings of the National Academy of Sciences of the United States of America: NATL ACAD SCIENCES114:44, s. 11769-117740027-84241091-6490
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Baker, Maggie
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Lindell, Stephen ...
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Zhou, Zhifeng
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Miller-Crews, Is ...
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Paukner, Annika
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Francesco Ferrar ...
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Razaqyar, Muslim ...
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Sommer, Wolfgang ...
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Lopez, Juan F.
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