A critical period of vulnerability to adolescent stress: epigenetic mediators in mesocortical dopaminergic neurons

Human Molecular Genetics
Minae NiwaAkira Sawa

Abstract

The molecular basis of vulnerability to stress during the adolescent period is largely unknown. To identify potential molecular mediators that may play a role in stress-induced behavioral deficits, we imposed social isolation on a genetically vulnerable mouse model. We report that 3-week (5-8 weeks of age) adolescent stress in combination with disrupted-in-schizophrenia 1 (Disc1) genetic risk elicits alterations in DNA methylation of a specific set of genes, tyrosine hydroxylase, brain-derived neurotrophic factor and FK506 binding protein 5. The epigenetic changes in the mesocortical dopaminergic neurons were prevented when animals were treated with a glucocorticoid receptor (GR) antagonist RU486 during social isolation, which implicates the role for glucocorticoid signaling in this pathological event. We define the critical period of GR intervention as the first 1-week period during the stress regimen, suggesting that this particular week in adolescence may be a specific period of maturation and function of mesocortical dopaminergic neurons and their sensitivity to glucocorticoids. Our study may also imply the clinical significance of early detection and prophylactic intervention against conditions associated with adolescent s...Continue Reading

References

Feb 16, 2005·Annual Review of Psychology·Avshalom CaspiRebecca L Shiner
Aug 15, 2006·Annual Review of Psychology·Megan Gunnar, Karina Quevedo
Aug 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Takatoshi HikidaAkira Sawa
Mar 21, 2008·Nature Reviews. Neuroscience·Sarah-Jayne Blakemore
Jul 9, 2008·Journal of Chemotherapy·Ling He, Bian-Sheng Ji
Oct 24, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sanbing ShenDavid St Clair
Nov 13, 2008·Nature Reviews. Neuroscience·Tomás PausJay N Giedd
May 30, 2009·Journal of Neurochemistry·Pheona M RadcliffeA William Tank
Feb 16, 2010·Nature Immunology·Pornpimon AngkasekwinaiChen Dong
Nov 19, 2011·Nature Reviews. Neuroscience·Nicholas J Brandon, Akira Sawa
Jan 12, 2013·Biological Psychiatry·Jennifer L Thompson, Stephanie L Borgland

❮ Previous
Next ❯

Citations

Oct 5, 2016·Social Cognitive and Affective Neuroscience·Fanny Gollier-BriantEric Artiges
Aug 1, 2018·International Journal of Molecular Sciences·Larisa RyskalinFrancesco Fornai
Oct 12, 2016·Neural Plasticity·Paula MoranColm O'Tuathaigh
Dec 16, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Olivia H CoxRichard S Lee
May 19, 2018·Journal of Pharmacological Sciences·Sedona LockhartMinae Niwa
Jul 30, 2018·Trends in Ecology & Evolution·Nathan W Bailey, Allen J Moore
Nov 25, 2021·Science Advances·Mei-Fang XiaoPaul F Worley

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.