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 journalArticlepeer-review

202 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

All Science Journal Classification (ASJC) codes

  • General

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