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Science 339 (6117): 335-339

Copyright © 2013 by the American Association for the Advancement of Science

Adolescent Stress–Induced Epigenetic Control of Dopaminergic Neurons via Glucocorticoids

Minae Niwa,1,2,3 Hanna Jaaro-Peled,2 Stephanie Tankou,2 Saurav Seshadri,2 Takatoshi Hikida,2,4 Yurie Matsumoto,1,3 Nicola G. Cascella,2 Shin-ichi Kano,2 Norio Ozaki,3 Toshitaka Nabeshima,1,5,6,* Akira Sawa2,*

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.

1 Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, Nagoya 468-8503, Japan.
2 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
3 Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya 464-8601, Japan.
4 Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
5 Academic Frontier Project for Private University, Comparative Cognitive Science Institution, Meijo University, Nagoya 468-8503, Japan.
6 Department of Regional Pharmaceutical Care and Science, Meijo University, Nagoya 468-8503, Japan.

* To whom correspondence should be addressed. E-mail: asawa1{at} (A.S.); tnabeshi{at} (T.N.)

Hormones and the Social Brain.
B. S. McEwen (2013)
Science 339, 279-280
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