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Increasing norepinephrine stabilizes breathing patterns in a mouse model of Rett Syndrome

Grard Hilaire of the National Center for Scientific Research (CNRS), Laurent Villard of the French National Institutes of Health (INSERM) and Jan-Marino Ramirez of the University of Chicago and colleagues report in the December 14th, 2005 issue of the Journal of Neuroscience that the breathing disturbances in a mouse model of Rett Syndrome originate, at least in part, from a deficiency in norepinephrine and serotonin in a specific brain region called the medulla. This work was funded in part by the Rett Syndrome Research Foundation (RSRF).

Rett Syndrome (RTT) is a severe neurological disorder diagnosed almost exclusively in girls. Children with RTT appear to develop normally until 6 to 18 months of age, when they enter a period of regression, losing speech and motor skills. Most develop repetitive hand movements, seizures and extreme motor control problems. Irregular breathing patterns characterized by intermittent breath holding, hyperventilation and air swallowing are a particularly devastating symptom of the disorder. In some cases the irregular breathing can lead to death due to sudden respiratory arrhythmia. It is worthwhile to note that individuals with drastic respiratory alterations can spontaneously display transient periods of normal breathing and that breathing can normalize during sleep. RTT leaves its victims profoundly disabled, requiring maximum assistance with every aspect of daily living. There is no cure.

At birth, the mouse model of RTT exhibits typical breathing and normal content of norepinephrine in the medulla. The medulla is a section of the brainstem that is responsible for autonomic function (all the processes in the body that we take for granted like breathing, digestion, cardiac function, temperature control). Between one and two months of age, the mice displayed breathing disturbances that worsened until fatal respiratory arrest at about two months of age. The breathing disturbances were highly variable from mouse to mous
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Contact: Monica Coenraads
monica@rsrf.org
203-445-9233
Rett Syndrome Research Foundation
13-Dec-2005


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