Cited by 228Epigenetics and DNA MethylationStress Responses and CortisolBirth, Development, and Health

Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation

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Provençal, Nadine, Arloth, Janine, Cattaneo, Annamaria, Anacker, Christoph, Cattane, Nadia, Wiechmann, Tobias, Röh, Simone, Ködel, Maik +12 more·2020·Proceedings of the National Academy of Sciences

Abstract

Significance: Prenatal stress exposure is associated with a wide range of health problems later in life. This may be mediated in part via glucocorticoid (GC) exposure during fetal development known to impact neurogenesis and induce epigenetic changes. Using a human fetal hippocampal progenitor cell line to assess the effects of GCs, we observe that exposure to GCs early during neurogenesis results in lasting changes in DNA methylation (DNAm). Lasting DNAm alterations are associated with significantly enhanced transcriptional response to a subsequent GC exposure. Our data suggest that early exposure to GCs changes the set point of future transcriptional responses to stress by inducing lasting DNAm changes. Such altered set points may relate to differential vulnerability to stress exposure later in life.

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Crossref · 10.1073/pnas.1820842116

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37 of 37 references verified0 citation errors · 0 not checkable

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  • Lasting changes in DNA methylation result in an altered set-point for transcriptional changes of FKBP5 upon subsequent GR activation.

    “Such lasting changes in DNAm result in an altered set-point for transcriptional changes of FKBP5 upon subsequent GR activation. 55 , 69 , 72”

    From Epigenetics and depression (2019) · cites this paper as [55]

  • Glucocorticoid-induced DNA methylation changes are long-lasting and prime the stress response for future exposure.

    “Subsequent post-differentiation exposure to GCs resulted in robust transcriptional changes in the HPCs that were initially treated during proliferation and differentiation, indicating that GC induced DNAm changes are long-lasting and prime the stress response for future exposure.”

    From Epigenetics and depression (2019) · cites this paper as [55]

  • The differentially methylated regions in that HPC model were enriched for the binding motif of the glucocorticoid receptor.

    “Furthermore, the DMRs were enriched for the binding motif of the glucocorticoid receptor (GR), a key modulator of the hypothalamus-pituitary-adrenal (HPA) axis.”

    From Epigenetics and depression (2019) · cites this paper as [55]

  • In a human hippocampal progenitor cell line model, exposure to glucocorticoids during differentiation and proliferation induced long-lasting DNA methylation changes.

    “In a model of stress using a human hippocampal progenitor cell line (HPCs), exposure to glucocorticoids (GCs) during differentiation and proliferation induced long-lasting DNAm changes.”

    From Epigenetics and depression (2019) · cites this paper as [55]

  • In human models, environmental factors can induce epigenetic changes.

    “In human models, there is also evidence of environmental factors inducing epigenetic changes. 55”

    From Epigenetics and depression (2019) · cites this paper as [55]

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Authors
Provençal, N., Arloth, J., Cattaneo, A., Anacker, C., Cattane, N., Wiechmann, T., Röh, S., Ködel, M., Klengel, T., Czamara, D., Müller, N. S., Lahti, J., PREDO team, Räikkönen, K., Pariante, C. M., Binder, E. B., Kajantie, E., Hämäläinen, E., Villa, P., & Laivuori, H.
Affiliations
  • Simon Fraser University (CA)
  • Helmholtz Munich (DE)
  • King's College London (GB)
  • Research Foundation For Mental Hygiene (US)
  • Centro San Giovanni di Dio Fatebenefratelli (IT)
  • Max Planck Institute of Psychiatry (DE)
  • Harvard University (US)
  • University of Helsinki (FI)
  • Emory University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2019-08-09
Volume
117
Issue
38
Pages
23280-23285
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2968811349
Cited by
209
References
37
Citations by year
2026: 16 · 2025: 22 · 2024: 32 · 2023: 34 · 2022: 28 · 2021: 46 · 2020: 24 · 2019: 7
FWCI
10.17
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • Site cant be reached (submittedVersion, other-oa)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Funders
  • National Institute for Health and Care Research (NIHR201376, NF-SI-0616-10074)
  • Canadian Institutes of Health Research
  • Medical Research Council (MR/N029488/1)
  • National Institute of Mental Health (K99MH108719, R00MH108719)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD088931)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
glucocorticoids, prenatal stress, hippocampal neurogenesis, DNA methylation, epigenetics, hippocampal progenitor cells, stress response, differentially methylated sites, umbilical cord blood, mental illness, fetal brain development
MeSH terms
Female, Gene Expression Regulation, Glucocorticoids, Hippocampus, Humans, Male, Pregnancy, Prenatal Exposure Delayed Effects, Stress, Physiological, Cohort Studies, DNA Methylation, Neurogenesis

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