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Adolescent Stress—Induced Epigenetic Control of Dopaminergic Neurons via Glucocorticoids
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Adolescent Stress—Induced Epigenetic Control of Dopaminergic Neurons via Glucocorticoids
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Journal Article
Adolescent Stress—Induced Epigenetic Control of Dopaminergic Neurons via Glucocorticoids
2013
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Adults
/ Affective Disorders, Psychotic - genetics
/ Affective Disorders, Psychotic - metabolism
/ Animals
/ distress
/ DNA
/ dopamine
/ Dopaminergic Neurons - metabolism
/ Emotions
/ genes
/ Genetics
/ Glucocorticoids - metabolism
/ Humans
/ Mice
/ mutants
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - metabolism
/ Neurons
/ Prions
/ Stress, Psychological - genetics
/ Stress, Psychological - metabolism
/ Stresses
