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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Corticosterone / administration & dosage
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Corticosterone / blood
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Corticosterone / pharmacology*
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Disease Models, Animal
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Female
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Gene Expression Regulation
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Glucocorticoids / metabolism*
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Immediate-Early Proteins / genetics
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Life Expectancy
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Male
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Methyl-CpG-Binding Protein 2 / genetics
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Mice
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Mifepristone / metabolism
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Mifepristone / pharmacology*
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Motor Activity / drug effects
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Protein Serine-Threonine Kinases / genetics
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Receptors, Glucocorticoid / antagonists & inhibitors
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Receptors, Glucocorticoid / metabolism*
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Rett Syndrome / genetics
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Rett Syndrome / physiopathology*
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Rotarod Performance Test
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Tacrolimus Binding Proteins / genetics
Substances
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Glucocorticoids
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Immediate-Early Proteins
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Mecp2 protein, mouse
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Methyl-CpG-Binding Protein 2
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Receptors, Glucocorticoid
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Mifepristone
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Protein Serine-Threonine Kinases
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serum-glucocorticoid regulated kinase
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Tacrolimus Binding Proteins
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tacrolimus binding protein 5
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Corticosterone