Resilience to Social Stress Coincides with Functional DNA Methylation of the Crf Gene in Adult Mice

Overview

Journal Nat Neurosci

Date 2010 Oct 5

PMID 20890295

Citations 200

Authors

Evan Elliott

Gili Ezra-Nevo

Limor Regev

Adi Neufeld-Cohen

Alon Chen

Affiliations

Soon will be listed here.

Abstract

DNA methylation regulates gene transcription and has been suggested to encode psychopathologies derived from early life stress. We found that methylation regulated the expression of the Crf (also known as Crh) gene and that chronic social stress in adult mice induced long-term demethylation of this genomic region. Demethylation was observed only in the subset of defeated mice that displayed social avoidance and site-specific knockdown of Crf attenuated the stress-induced social avoidance.

Citing Articles

Prenatal maternal life adversity impacts on learning and memory in offspring: implication to transgenerational epigenetic inheritance.

Adeline Dorothy P, Rajan K Front Neurosci. 2025; 19:1518046.

PMID: 40018363 PMC: 11865043. DOI: 10.3389/fnins.2025.1518046.

Endocrine Disrupting Toxicity of Bisphenol A and Its Analogs: Implications in the Neuro-Immune Milieu.

Buoso E, Masi M, Limosani R, Oliviero C, Saeed S, Iulini M J Xenobiot. 2025; 15(1.

PMID: 39846545 PMC: 11755641. DOI: 10.3390/jox15010013.

Epigenetic Modifications and Neuroplasticity in the Pathogenesis of Depression: A Focus on Early Life Stress.

Benatti B, Adiletta A, Sgado P, Malgaroli A, Ferro M, Lamanna J Behav Sci (Basel). 2024; 14(10).

PMID: 39457754 PMC: 11504006. DOI: 10.3390/bs14100882.

Neuroendocrine and cellular mechanisms in stress resilience: From hormonal influence in the CNS to mitochondrial dysfunction and oxidative stress.

Bhattacharya A, Chakraborty M, Chanda A, Alqahtani T, Kumer A, Dhara B J Cell Mol Med. 2024; 28(7):e18220.

PMID: 38509751 PMC: 10955164. DOI: 10.1111/jcmm.18220.

The Psychoneuroimmunological Model of Moral Distress and Health in Healthcare Workers: Toward Individual and System-Level Solutions.

Seiler A, Milliken A, Leiter R, Blum D, Slavich G Compr Psychoneuroendocrinol. 2024; 17:100226.

PMID: 38482488 PMC: 10935511. DOI: 10.1016/j.cpnec.2024.100226.

References

McGowan P, Sasaki A, DAlessio A, Dymov S, Labonte B, Szyf M . Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009; 12(3):342-8. PMC: 2944040. DOI: 10.1038/nn.2270. View

Joels M, Baram T . The neuro-symphony of stress. Nat Rev Neurosci. 2009; 10(6):459-66. PMC: 2844123. DOI: 10.1038/nrn2632. View

Roth T, Lubin F, Funk A, Sweatt J . Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry. 2009; 65(9):760-9. PMC: 3056389. DOI: 10.1016/j.biopsych.2008.11.028. View

Murgatroyd C, Patchev A, Wu Y, Micale V, Bockmuhl Y, Fischer D . Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci. 2009; 12(12):1559-66. DOI: 10.1038/nn.2436. View

Aguilera G, Kiss A, Liu Y, Kamitakahara A . Negative regulation of corticotropin releasing factor expression and limitation of stress response. Stress. 2007; 10(2):153-61. DOI: 10.1080/10253890701391192. View

de Kloet E, Joels M, Holsboer F . Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005; 6(6):463-75. DOI: 10.1038/nrn1683. View

Bale T, Vale W . CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol. 2004; 44:525-57. DOI: 10.1146/annurev.pharmtox.44.101802.121410. View

Mueller B, Bale T . Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci. 2008; 28(36):9055-65. PMC: 2731562. DOI: 10.1523/JNEUROSCI.1424-08.2008. View

Ma D, Jang M, Guo J, Kitabatake Y, Chang M, Pow-anpongkul N . Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science. 2009; 323(5917):1074-7. PMC: 2726986. DOI: 10.1126/science.1166859. View

10.

Tsankova N, Berton O, Renthal W, Kumar A, Neve R, Nestler E . Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci. 2006; 9(4):519-25. DOI: 10.1038/nn1659. View

11.

McEwen B . Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007; 87(3):873-904. DOI: 10.1152/physrev.00041.2006. View

12.

Vale W, Spiess J, Rivier C, Rivier J . Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science. 1981; 213(4514):1394-7. DOI: 10.1126/science.6267699. View

13.

Zhang X, Odom D, Koo S, Conkright M, Canettieri G, Best J . Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci U S A. 2005; 102(12):4459-64. PMC: 555478. DOI: 10.1073/pnas.0501076102. View

14.

Krishnan V, Han M, Graham D, Berton O, Renthal W, Russo S . Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell. 2007; 131(2):391-404. DOI: 10.1016/j.cell.2007.09.018. View