Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity

摘要: Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from range debilitating physical symptoms, however, behavioral emotional symptoms also severely affect their quality life. Here, we present previously unreported clinically relevant affective dysfunction female heterozygous Mecp2tm1Tam mouse model RTT (129sv C57BL6 mixed background). The aberrant anxiety-related behavior Mecp2+/− mice were found to be reversible environmental enrichment (EE) 4 weeks age. effect exercise alone (via wheel running) was explored, providing first evidence that increased voluntary activity an animal beneficial for some phenotypes. mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating hypothalamic–pituitary–adrenal axis dysregulation. EE normalized basal serum hippocampal BDNF levels. enrichment-induced rescue appears independent transcriptional regulation MeCP2 targets Bdnf exon Crh. These findings provide new insight into role pathogenesis RTT, particular dysfunction. positive outcomes stimulation have implications development therapies targeting as well cognitive dimensions, this devastating disorder. © 2015 Wiley Periodicals, Inc. Develop Neurobiol,