Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids

Minae Niwa, Hanna Jaaro-Peled, Stephanie Tankou, Saurav Seshadri, Takatoshi Hikida, Yurie Matsumoto, Nicola G. Cascella, Shin Ichi Kano, Norio Ozaki, Toshitaka Nabeshima, Akira Sawa

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Environmental stressors during childhood and adolescence influence postnatal brain maturation and human behavioral patterns in adulthood. Accordingly, excess stressors result in adult-onset neuropsychiatric disorders. We describe an underlying mechanism in which glucocorticoids link adolescent stressors to epigenetic controls in neurons. In a mouse model of this phenomenon, a mild isolation stress affects the mesocortical projection of dopaminergic neurons in which DNA hypermethylation of the tyrosine hydroxylase gene is elicited, but only when combined with a relevant genetic risk for neuropsychiatric disorders. These molecular changes are associated with several neurochemical and behavioral deficits that occur in this mouse model, all of which are blocked by a glucocorticoid receptor antagonist. The biology and phenotypes of the mouse models resemble those of psychotic depression, a common and debilitating psychiatric disease.

Original languageEnglish
Pages (from-to)335-339
Number of pages5
JournalScience
Volume339
Issue number6117
DOIs
Publication statusPublished - 18-01-2013

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Dopaminergic Neurons
Epigenomics
Glucocorticoids
Glucocorticoid Receptors
Tyrosine 3-Monooxygenase
Psychiatry
Phenotype
Neurons
DNA
Brain
Genes

All Science Journal Classification (ASJC) codes

  • General

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Niwa, M., Jaaro-Peled, H., Tankou, S., Seshadri, S., Hikida, T., Matsumoto, Y., ... Sawa, A. (2013). Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids. Science, 339(6117), 335-339. https://doi.org/10.1126/science.1226931
Niwa, Minae ; Jaaro-Peled, Hanna ; Tankou, Stephanie ; Seshadri, Saurav ; Hikida, Takatoshi ; Matsumoto, Yurie ; Cascella, Nicola G. ; Kano, Shin Ichi ; Ozaki, Norio ; Nabeshima, Toshitaka ; Sawa, Akira. / Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids. In: Science. 2013 ; Vol. 339, No. 6117. pp. 335-339.
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Niwa, M, Jaaro-Peled, H, Tankou, S, Seshadri, S, Hikida, T, Matsumoto, Y, Cascella, NG, Kano, SI, Ozaki, N, Nabeshima, T & Sawa, A 2013, 'Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids', Science, vol. 339, no. 6117, pp. 335-339. https://doi.org/10.1126/science.1226931

Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids. / Niwa, Minae; Jaaro-Peled, Hanna; Tankou, Stephanie; Seshadri, Saurav; Hikida, Takatoshi; Matsumoto, Yurie; Cascella, Nicola G.; Kano, Shin Ichi; Ozaki, Norio; Nabeshima, Toshitaka; Sawa, Akira.

In: Science, Vol. 339, No. 6117, 18.01.2013, p. 335-339.

Research output: Contribution to journalArticle

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Niwa M, Jaaro-Peled H, Tankou S, Seshadri S, Hikida T, Matsumoto Y et al. Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids. Science. 2013 Jan 18;339(6117):335-339. https://doi.org/10.1126/science.1226931