TY - JOUR
T1 - Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids
AU - Niwa, Minae
AU - Jaaro-Peled, Hanna
AU - Tankou, Stephanie
AU - Seshadri, Saurav
AU - Hikida, Takatoshi
AU - Matsumoto, Yurie
AU - Cascella, Nicola G.
AU - Kano, Shin Ichi
AU - Ozaki, Norio
AU - Nabeshima, Toshitaka
AU - Sawa, Akira
PY - 2013/1/18
Y1 - 2013/1/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84872443390&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872443390&partnerID=8YFLogxK
U2 - 10.1126/science.1226931
DO - 10.1126/science.1226931
M3 - Article
C2 - 23329051
AN - SCOPUS:84872443390
SN - 0036-8075
VL - 339
SP - 335
EP - 339
JO - Science
JF - Science
IS - 6117
ER -