Dynamic DNA methylation programs persistent adverse effects of early-life stress

Autoři	MURGATROYD Chris PATCHEV Alexandre V WU Yonghe MICALE Vincenzo BOCKMUHL Yvonne FISCHER Dieter HOLSBOER Florian WOTJAK Carsten T ALMEIDA Osborne F X SPENGLER Dietmar
Rok publikování	2009
Druh	Článek v odborném periodiku
Časopis / Zdroj	Nature Neuroscience
Citace
Doi	http://dx.doi.org/10.1038/nn.2436
Obor	Neurologie, neurochirurgie, neurovědy
Klíčová slova	PITUITARY-ADRENAL AXIS; GENE-EXPRESSION; MOUSE MODEL; EPIGENETIC REGULATION; BDNF TRANSCRIPTION; RETT-SYNDROME; DISORDERS; ANXIETY; MECP2; BRAIN
Popis	Adverse early life events can induce long-lasting changes in physiology and behavior. We found that early-life stress (ELS) in mice caused enduring hypersecretion of corticosterone and alterations in passive stress coping and memory. This phenotype was accompanied by a persistent increase in arginine vasopressin (AVP) expression in neurons of the hypothalamic paraventricular nucleus and was reversed by an AVP receptor antagonist. Altered Avp expression was associated with sustained DNA hypomethylation of an important regulatory region that resisted age-related drifts in methylation and centered on those CpG residues that serve as DNA-binding sites for the methyl CpG-binding protein 2 (MeCP2). We found that neuronal activity controlled the ability of MeCP2 to regulate activity-dependent transcription of the Avp gene and induced epigenetic marking. Thus, ELS can dynamically control DNA methylation in postmitotic neurons to generate stable changes in Avp expression that trigger neuroendocrine and behavioral alterations that are frequent features in depression.