title: Epigenetic programming of the HPA axis: early life decides.
abstract: Stress during early life can impact the developing brain and increase vulnerability to mood disorders later in life. Here, we argue that epigenetic mechanisms can mediate the gene-environment dialogue in early life and give rise to persistent epigenetic programming of adult physiology eventually resulting in disease. Early life stress in mice leads to epigenetic marking of the arginine vasopressin (AVP) gene underpinning sustained expression and increased hypothalamic-pituitary-adrenal axis activity. This epigenetic memory is laid down in the parvocellular neurons of the paraventricular nucleus and involves Ca(2+)/calmodulin kinase-mediated phosphorylation of the methyl-CpG binding domain protein MeCP2 leading to dissociation from its DNA-binding site and derepression of the AVP gene. The reduced occupancy of MeCP2 during this early stage of life facilitates the development of hypomethylation at the AVP enhancer, which sustains derepression throughout later life and thereby serves to hardwire early life experiences. The sequential order of these events may represent a critical time window for the preventive therapy of severe trauma.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany. murgatroyd@mpipsykl.mpg.de
authors.forename: Chris
authors.initials: C
authors.lastname: Murgatroyd
authors.forename: Dietmar
authors.initials: D
authors.lastname: Spengler
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology / Q000503:physiopathology*; D008426:Maternal Deprivation; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D051379:Mice; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D051381:Rats
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D001127:Arginine Vasopressin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2