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New insight about the source of anxiety in Rett syndrome

A peptide known to play a role in anxiety is overly plentiful in a mouse model of the inherited neurological disorder Rett syndrome and appears to underlie the anxiety-like behavior in these mice, said researchers from Baylor College of Medicine in a report that appears online in the Proceedings of the National Academy of Sciences. The finding could provide a clue to treatment for this symptom.

"This is one of the first symptoms that we can link to a molecular cause," said Dr. Huda Zoghbi, professor of pediatrics, neurology and molecular and human genetics at Baylor College of Medicine and a Howard Hughes Medical Institute investigator. "Rett affects many parts of the nervous system, and patients have many symptoms; but we don't know if they happen all at once or if there is a cascade of events."

If the latter is true, then physicians might be able to intervene by halting or limiting the effect of the first symptoms to prevent secondary effects such as those that occur due to chronic anxiety.

The mouse model of Rett was developed in Zoghbi's laboratory where scientists also found that a mutation in the gene MeCP2 (methyl-CpG-binding protein 2) causes the disorder. Between the ages of six and 18 months, children with this disease become mentally retarded, wring their hands, have difficulty walking and breathing, and suffer from anxiety. The severity of the symptoms varies with the person.

"MeCP2 is a master regulator of other genes, like a foreman in a factory," said Bryan E. McGill, a BCM M.D./Ph.D. student studying in Zoghbi's laboratory. "Considered by itself, it cannot tell you about the molecular changes that lead to the phenotype (symptoms) we see in the children. Our goal has been to find the intermediaries in the process. We want to know what other genes MeCP2 is controlling. Then we have a better understanding of the molecular basis of the phenotype we see in children."

In their work, they found that CRH (cort
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Contact: Ross Tomlin
htomlin@bcm.edu
713-798-4710
Baylor College of Medicine
13-Nov-2006


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