title: Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids.
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.
authors: Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, Nagoya, Japan.
authors: Minae
authors: M
authors: Niwa
authors: Hanna
authors: H
authors: Jaaro-Peled
authors: Stephanie
authors: S
authors: Tankou
authors: Saurav
authors: S
authors: Seshadri
authors: Takatoshi
authors: T
authors: Hikida
authors: Yurie
authors: Y
authors: Matsumoto
authors: Nicola G
authors: NG
authors: Cascella
authors: Shin-ichi
authors: S
authors: Kano
authors: Norio
authors: N
authors: Ozaki
authors: Toshitaka
authors: T
authors: Nabeshima
authors: Akira
authors: A
authors: Sawa
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior; D041923:Adolescent Development; D000341:Affective Disorders, Psychotic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*
chemical_list: C412476:DISC1 protein, human; D005938:Glucocorticoids; D009419:Nerve Tissue Proteins