Novelty stress induces phospho‐acetylation of histone H3 in rat dentate gyrus granule neurons through coincident signalling via the N‐methyl‐d‐aspartate receptor and the glucocorticoid receptor: relevance for c‐fos induction
Abstract
The hippocampus plays an important role in novelty detection, stress‐related adaptation and learning and memory. However, it is unknown whether the response to novelty in the hippocampus involves induction of chromatin remodelling events known to be associated with transcriptional regulation. Here, we examined whether exposure to a novel environment, a mild psychological stressor, would affect the number of phospho‐acetylated histone H3‐positive [P(Ser10)‐Ac(Lys14)‐H3+] neurons in the rat hippocampus. We show that: (i) the stressful situation induced a marked increase in the number of P(Ser10)‐Ac(Lys14)‐H3+ neurons, specifically in the dentate gyrus; (ii) the stress‐induced rise in P(Ser10)‐Ac(Lys14)‐H3+ neurons occurred in the dentate gyrus throughout the rostro‐caudal axis of the hippocampus, but they were exclusively located in the middle and superficial aspects of the granular cell layer of the upper blade of the dentate gyrus; (iii) antagonism of NMDA or glucocorticoid receptors, but not antagonism of mineralocorticoid receptors or inhibition of nitric oxide synthesis, attenuated the stress‐induced response; (iv) combined blockade of NMDA and glucocorticoid receptors ablated the stress‐induced histone modification response; (v) moreover, this combined blockade also abolished the induction of the P(Ser10)‐Ac(Lys14)‐H3‐associated gene product c‐fos after stress; (vi) administration of corticosterone to unstressed rats did not affect histone H3 phospho‐acetylation. Thus, novelty stress induces chromatin remodelling and c‐fos induction in mature dentate neurons through concurrent signalling via the NMDA receptor and the glucocorticoid receptor.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Rats exposed to novelty stress showed induction of H3S10p at the c-fos promoter site in the dentate gyrus.
“Rats exposed to novelty stress also showed an induction of H3S10p at the c-fos promoter site in the dentate gyrus.186”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [186]
Cites
The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.
Tsien, J. Z., Huerta, P. T., & Tonegawa, S. (1996) · Cell · doi:10.1016/s0092-8674(00)81827-9 · Cited by 1,782 · cited 2× · see citing works
“long-term potentiation, synaptogenesis (Sheng and Kim 2002; Nikonenko et al. 2003), anxiety (Korte 2001), HPA axis stress hormone regulation (Reul and De Kloet 1985; De Kloet et al. 1998; Bilang-Bleuel et al. 2005) and learning and memory processes ( Tsien et al. 1996; De Kloet et al. 1998; Korte 2001; Bachmann et al.…”
BackgroundSignaling to Chromatin through Histone Modifications
Cheung, P., Allis, C. D., & Sassone-Corsi, P. (2000) · Cell · doi:10.1016/s0092-8674(00)00118-5 · Cited by 989 · see citing works
Epigenetic mechanisms in memory formation
Levenson, J. M., & Sweatt, J. D. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1604 · Cited by 767 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Coping with the Forced Swim Stressor: Towards Understanding an Adaptive Mechanism
de Kloet, E. R., & Molendijk, M. L. (2016) · Neural Plasticity · doi:10.1155/2016/6503162 · Cited by 353 · see citing works
Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators
Kaliman, P., Álvarez-López, M. J., Cosín-Tomás, M., Rosenkranz, M. A., Lutz, A., & Davidson, R. J. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.11.004 · Cited by 300 · see citing works
Regulation of hippocampal H3 histone methylation by acute and chronic stress
Hunter, R. G., McCarthy, K. J., Milne, T. A., Pfaff, D. W., & McEwen, B. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911143106 · Cited by 290 · see citing works
Yuan, M., Yang, B., Rothschild, G., Mann, J. J., Sanford, L. D., Tang, X., Huang, C., Wang, C., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01519-z · Cited by 246 · see citing works
“Rats exposed to novelty stress also showed an induction of H3S10p at the c-fos promoter site in the dentate gyrus.(186) To date, few studies have investigated the relationship between histone phosphorylation and MDD.”
BackgroundRoozendaal, B., Hernandez, A., Cabrera, S. M., Hagewoud, R., Malvaez, M., Stefanko, D. P., Haettig, J., & Wood, M. A. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5717-09.2010 · Cited by 233 · see citing works
Epigenetics of stress adaptations in the brain
Stankiewicz, A. M., Swiergiel, A. H., & Lisowski, P. (2013) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.07.003 · Cited by 220 · see citing works
Reul, J. M. H. M. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00005 · Cited by 147 · see citing works
Self-citationCollins, A., Hill, L. E., Chandramohan, Y., Whitcomb, D., Droste, S. K., & Reul, J. M. H. M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004330 · Cited by 145 · see citing works
Self-citationSchroeder, F. A., Penta, K. L., Matevossian, A., Jones, S. R., Konradi, C., Tapper, A. R., & Akbarian, S. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.15 · Cited by 139 · see citing works
Schoenfeld, T. J., Rada, P., Pieruzzini, P. R., Hsueh, B., & Gould, E. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.5352-12.2013 · Cited by 138 · see citing works
Effects of the histone deacetylase inhibitor sodium butyrate in models of depression and anxiety
Gundersen, B. B., & Blendy, J. A. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.04.008 · Cited by 112 · see citing works
Kolber, B. J., Wieczorek, L., & Muglia, L. J. (2008) · Stress · doi:10.1080/10253890701821081 · Cited by 106 · see citing works
Epigenetic mechanisms in stress and adaptation
Mifsud, K. R., Gutièrrez-Mecinas, M., Trollope, A. F., Collins, A., Saunderson, E. A., & Reul, J. M. H. M. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.06.005 · Cited by 100 · see citing works
Self-citationDynamically changing effects of corticosteroids on human hippocampal and prefrontal processing
Henckens, M. J. A. G., Pu, Z., Hermans, E. J., van Wingen, G. A., Joëls, M., & Fernández, G. (2012) · Human Brain Mapping · doi:10.1002/hbm.21409 · Cited by 80 · see citing works
Stress, epigenetic control of gene expression and memory formation
Trollope, A. F., Gutièrrez-Mecinas, M., Mifsud, K. R., Collins, A., Saunderson, E. A., & Reul, J. M. H. M. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2011.03.022 · Cited by 69 · see citing works
Self-citationEffects of Novelty Stress on Hippocampal Gene Expression, Corticosterone and Motor Activity in Mice
Kurumaji, A., Umino, M., & Nishikawa, T. (2011) · Neuroscience Research · doi:10.1016/j.neures.2011.06.006 · Cited by 18 · see citing works
- Authors
- Chandramohan, Y., Droste, S. K., & Reul, J. M. H. M.
- Affiliations
- University of Bristol (GB)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2006-12-05
- Volume
- 101
- Issue
- 3
- Pages
- 815-828
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1934033863
- Cited by
- 117
- References
- 3
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 8 · 2016: 7 · 2015: 5 · 2014: 9 · 2013: 18 · 2012: 2
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- novelty stress, dentate gyrus granule cells, NMDA receptor, glucocorticoid receptor, c-fos induction, chromatin remodeling, hippocampus, stress response, corticosterone, nitric oxide
- MeSH terms
- Acetylation, Analysis of Variance, Animals, Behavior, Animal, Corticosterone, Dose-Response Relationship, Radiation, Drug Interactions, Histones, Light, Male, Neurons, Receptors, Glucocorticoid, Stress, Psychological, Time Factors, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Rats, Wistar, Excitatory Amino Acid Antagonists, Dentate Gyrus, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
