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From Medicineworld.org: Cause Of Breathing Problems In Rett Syndrome Children

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Cause Of Breathing Problems In Rett Syndrome Children


Cause Of Breathing Problems In Rett Syndrome Children Child with Rett syndrome
A multi-institutional team, led by University of Chicago researchers, has taken a crucial step toward understanding and treating Rett syndrome (RS), a rare and often misdiagnosed neurodevelopmental disorder that affects 1 in 10,000 children, mostly females.

As per a research findings published in the December 14, 2005, issue of the Journal of Neuroscience, the scientists describe in a mouse model for RS the source of erratic breathing, which has important implications for children with RS.

Along with breathing problems, RS causes slowed brain and head growth, mental retardation, seizures, gait abnormalities, and handwringing.

"It is absolutely tragic for the family," said Jan-Marino Ramirez, professor of organismal biology and anatomy at Chicago and lead author of the paper. "It's a progressive disease that shows no mercy".

In order to study the breathing pattern more closely, Ramirez and his team showed that mice with the RS gene exhibit the same behavior as children: They breathe irregularly and stop breathing often.

According to Ramirez, one hypothesis that has dominated the thinking of a number of clinicians is that the erratic breathing is due to cortical problems. "It's as if they want to stop breathing," he said. "Some clinicians went that far to suggest that it could be pleasurable for the child to stop breathing all of the time because they get a euphoric high. Or they do this because they're agitated".

However, the scientists traced the problem not to the cortex but to the breathing center itself--in the medulla. The scientists isolated the breathing center from mutant mice and were able to demonstrate that the same erratic breathing pattern, which is so characteristic for RS, also was expressed in the isolated brain tissue, revealing the breathing center as the source of the problem.

They also found, specifically in the breathing center, a significantly decreased amount of the neuromodulator norepinephrine.

When Ramirez's team added norepinephrine to the isolated breathing center, the breathing pattern normalized. "It became exactly as regular as the control--this was amazing," he said. "This experiment shows that the breathing problem can potentially be treated because you can compensate for the missing neuromodulatory drive".

While Ramirez's team worked with the brain tissue, his colleagues in France studied the animal.

Eventhough they found the disturbance specifically in the medulla, a number of of those neurons project to other targets in the brain, which may explain why a number of other functions are affected.

Scientists noted that the disturbance in the breathing rhythm of the tissue occurs early on, before the animal exhibits breathing problems. They suggest that the nervous system may compensate initially for the loss of norepinephrine, which may be why breathing appears normal at the behavioral level. However, the deficiency in norepinephrine eventually disturbs other neuromodulators, including serotonin and substance P. As other modulatory systems become disrupted there will be a cascade of physiological problems in the animal's developmental and autonomic systems, including the obvious disturbances in the breathing behavior itself.

According to Ramirez, it is not known how the mutation on the MECP2 gene, which was linked to RS in 1999, leads to the disturbance of the norepinephrine. "This is obviously one of the next issues that needs to be addressed in our experiments".

Ramirez also plans to start screening medications already on the market to treat the erratic breathing of the animal model, looking specifically at those drugs that treat both neural systems: norepinephrine and serotonin. (Substance P also will be affected since it is located in the same nerve cells as serotonin.).

Prozac, for example, is often prescribed to treat depression by boosting serotonin levels, as well as other drugs currently are used for attention deficit hyperactivity disorder that boost both serotonin and norepinephrine levels.

Researchers are eager to discover whether treating the erratic breathing of RS will affect any of the other problems associated with the disorder.

"I think it's going to have a wider effect," Ramirez said, "because norepinephrine, serotonin and substance P are not only involved in breathing control, they're also involved in a number of other functions, including motor control, which may help with the handwringing or if we are lucky, possibly also their walking.

"The breathing center is just one of the disturbed functions," he added. "It's the tell tale sign".

Ramirez also plans to further investigate why these neurons are not releasing enough norepinephrine. "By understanding any of these neuromodulators, you'll better understand a lot of childhood disorders".

Texas scientists, headed by Huda Zoghbi, located the mutated RS gene, MECP2, on the X chromosome in 1999. Since females have two X chromosomes, the normal version of the gene can compensate for much of the dysfunction. For boys there is no compensation; males die young, within the first year of life.

Severity of RS can vary. In some, RS is so serious that the child can no longer talk, sit or walk. A number of children with RS die before they reach their teenage years, and breathing abnormalities are thought to be the leading cause.

The research at the University of Chicago was funded by the Rett Syndrome Research Foundation. Other institutions involved in the study are: Centre National de la Recherche Scientifique, Universite de la Mediterranee, Instituto Politecnico Nacional, Northwestern University, Hôpital d'Enfants de la Timone and the Medical College of Wisconsin.


Source: University of Chicago Hospitals


Did you know?
A multi-institutional team, led by University of Chicago researchers, has taken a crucial step toward understanding and treating Rett syndrome (RS), a rare and often misdiagnosed neurodevelopmental disorder that affects 1 in 10,000 children, mostly females. As per a research findings published in the December 14, 2005, issue of the Journal of Neuroscience, the scientists describe in a mouse model for RS the source of erratic breathing, which has important implications for children with RS.

Medicineworld.org: Cause Of Breathing Problems In Rett Syndrome Children

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