Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Early-life stress can leave persistent epigenetic marks that may modulate vulnerability to psychiatric conditions later in life, including anxiety, depression and stress-related disorders. These are complex disorders with both environmental and genetic influences contributing to their etiology. Methyl-CpG Binding Protein 2 (MeCP2) has been attributed a key role in the control of neuronal activity-dependent gene expression and is a master regulator of experience-dependent epigenetic programming. Moreover, mutations in the<jats:italic>MECP2</jats:italic>gene are the primary cause of Rett syndrome and, to a lesser extent, of a range of other major neurodevelopmental disorders. Here, we aim to study the interaction of MeCP2 with early-life stress in variables known to be affected by this environmental manipulation, namely anxiety-like behavior and activity of the underlying neural circuits.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Using<jats:italic>Mecp2</jats:italic>heterozygous and wild-type female mice we investigated the effects of the interaction of<jats:italic>Mecp2</jats:italic>haplodeficiency with maternal separation later in life, by assessing anxiety-related behaviors and measuring concomitant c-FOS expression in stress- and anxiety-related brain regions of adolescent females. Moreover, arginine vasopressin and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus were analyzed for neuronal activation.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In wild-type mice, maternal separation caused a reduction in anxiety-like behavior and in the activation of the hypothalamic paraventricular nucleus, specifically in corticotropin-releasing hormone-positive cells, after the elevated plus maze. This effect of maternal separation was not observed in<jats:italic>Mecp2</jats:italic>heterozygous females that per se show decreased anxiety-like behavior and concomitant decreased paraventricular nuclei activation.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our data supports that MeCP2 is an essential component of HPA axis reprogramming and underlies the differential response to anxiogenic situations later in life.</jats:p></jats:sec>