For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
93
views
37
references
 Top references
cited by
280
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      1,212
      similar
       All similar
      • Record: found
      • Abstract: not found
      • Article: not found

      Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A-inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Epigenetic programming by maternal behavior.

          Ian Weaver, Nadia Cervoni, Frances Champagne … (2004)
          Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.
          Article 0 comments Cited 1326 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life.

            Ian Weaver, Frances Champagne, Shelley Brown … (2005)
            Stress responses in the adult rat are programmed early in life by maternal care and associated with epigenomic marking of the hippocampal exon 1(7) glucocorticoid receptor (GR) promoter. To examine whether such epigenetic programming is reversible in adult life, we centrally infused the adult offspring with the essential amino acid L-methionine, a precursor to S-adenosyl-methionine that serves as the donor of methyl groups for DNA methylation. Here we report that methionine infusion reverses the effect of maternal behavior on DNA methylation, nerve growth factor-inducible protein-A binding to the exon 1(7) promoter, GR expression, and hypothalamic-pituitary-adrenal and behavioral responses to stress, suggesting a causal relationship among epigenomic state, GR expression, and stress responses in the adult offspring. These results demonstrate that, despite the inherent stability of the epigenomic marks established early in life through behavioral programming, they are potentially reversible in the adult brain.
            Article 0 comments Cited 189 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Dopamine release in response to a psychological stress in humans and its relationship to early life maternal care: a positron emission tomography study using [11C]raclopride.

              Jens C Pruessner, Frances Champagne, Michael Meaney … (2004)
              Mesolimbic dopamine is thought to play a role in the processing of rewards. However, animal studies also demonstrate dopamine release in response to aversive stressful stimuli. Also, in animal studies, disruptions of the mother-infant relationship have been shown to have long-lasting effects on the mesolimbic dopamine system and the hypothalamic-pituitary adrenal axis. We therefore investigated dopamine release in response to stress in human subjects, considering the relationship to early life parental care. We screened 120 healthy young college students for parental care in early life using a combination of telephone interviews and questionnaires. Five students from the top end and five students from the bottom end of the parental care distribution were then invited for a positron emission tomography study using [11C]raclopride and a psychosocial stress task. The psychosocial stressor caused a significant release of dopamine in the ventral striatum as indicated by a reduction in [11C]raclopride binding potential in the stress versus resting condition in subjects reporting low parental care. Moreover, the magnitude of the salivary cortisol response to stress was significantly correlated with the reduction in [11C]raclopride binding in the ventral striatum (r = 0.78), consistent with a facilitating effect of cortisol on dopamine neuron firing. These data suggest that aversive stressful events can be associated with mesolimbic dopamine release in humans, and that the method presented here may be useful to study the effects of early life events on neurobiological stress systems.
              Article 0 comments Cited 160 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: Nature Neuroscience
                Abbreviated Title: Nat Neurosci
                Publisher: Springer Science and Business Media LLC
                ISSN (Print): 1097-6256
                ISSN (Electronic): 1546-1726
                Publication date Created: March 2009
                Publication date (Electronic): February 22 2009
                Publication date (Print): March 2009
                Volume: 12
                Issue: 3
                Pages: 342-348
                Article
                DOI: 10.1038/nn.2270
                PMC ID: 2944040
                PubMed ID: 19234457
                SO-VID: cd1f48ae-078b-4b3b-9de1-c97db4b0afda
                Copyright © © 2009
                License:

                http://www.springer.com/tdm

                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content1,212

                See all similar

                Cited by783

                See all cited by

                Most referenced authors691

                See all reference authors