title: Pharmacological interference with the glucocorticoid system influences symptoms and lifespan in a mouse model of Rett syndrome.
abstract: Rett syndrome (RTT) is caused by loss-of-function mutations in the X-linked gene MECP2 coding for methyl CpG-binding protein 2 (MeCP2). This protein can act as transcriptional repressor, and we showed in a previous study that glucocorticoid-inducible genes are up-regulated in an RTT mouse model and that these genes are direct MeCP2 targets. Here, we report that pharmacological intervention with the glucocorticoid system has an impact on the symptoms and lifespan in an RTT mouse model. Our data support a functional implication of the stress hormone system in RTT and suggest this hormone system as potential therapeutic target.
authors.affiliation: Department of Laboratory Medicine, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Klinikgatan 26, 221 84 Lund, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Braun
authors.forename: Denise
authors.initials: D
authors.lastname: Kottwitz
authors.forename: Ulrike A
authors.initials: UA
authors.lastname: Nuber
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics; D008017:Life Expectancy; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D051379:Mice; D015735:Mifepristone / Q000378:metabolism / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015518:Rett Syndrome / Q000235:genetics / Q000503:physiopathology*; D045442:Rotarod Performance Test; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099159:Tacrolimus Binding Protein 5
chemical_list: D003345:Corticosterone; D005938:Glucocorticoids; D017874:Immediate-Early Proteins; D051783:Methyl-CpG-Binding Protein 2; D015735:Mifepristone; D017346:Protein Serine-Threonine Kinases; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099159:Tacrolimus Binding Protein 5; C497393:Mecp2 protein, mouse