Pharmacological interference with the glucocorticoid system influences symptoms and lifespan in a mouse model of Rett syndrome

• Published in: Human molecular genetics Vol. 21; no. 8; pp. 1673 - 1680
• Main Authors: BRAUN, Sebastian, KOTTWITZ, Denise, NUBER, Ulrike A
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15-04-2012
• Subjects: Animal models; Animals; Basic Medicine; Biological and medical sciences; Corticosterone - administration & dosage; Corticosterone - blood; Corticosterone - pharmacology; Data processing; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genetics of eukaryotes. Biological and molecular evolution; Glucocorticoids; Glucocorticoids - metabolism; Hormones; Immediate-Early Proteins - genetics; Life Expectancy; Life span; Male; MeCP2 protein; Medical and Health Sciences; Medical Genetics; Medical sciences; Medicin och hälsovetenskap; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Methyl-CpG binding protein; Methyl-CpG-Binding Protein 2 - genetics; Mice; Mifepristone - metabolism; Mifepristone - pharmacology; Molecular and cellular biology; Motor Activity - drug effects; Mutation; Neurology; Protein-Serine-Threonine Kinases - genetics; Receptors, Glucocorticoid - antagonists & inhibitors; Receptors, Glucocorticoid - metabolism; Repressors; Rett syndrome; Rett Syndrome - genetics; Rett Syndrome - physiopathology; Rotarod Performance Test; Stress; Tacrolimus Binding Proteins - genetics; Transcription; X chromosome; Animal model; Nervous system diseases; Rodentia; Longevity; Glucocorticoid; Genetic disease; Cerebral disorder; Symptomatology; Vertebrata; Lifetime; Mammalia; Mouse; Central nervous system disease; Rett syndrome; Genetics; Degenerative disease
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddr602

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.