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

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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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Niwa, M., Jaaro-Peled, H., Tankou, S., Seshadri, S., Hikida, T., Matsumoto, Y., Cascella, N. G., Kano, S. I., Ozaki, N., Nabeshima, T., & 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