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Researchers Reversed Learning Deficits in Down-Syndrome Mice

Update Date: Sep 04, 2013 02:02 PM EDT

Down syndrome is a genetic disorder in which the individual is born with three copies of chromosome 21 instead of two. The trisomy then leads to the production of multiple copies of the genes located on this chromosome. As a result, people with Down syndrome have difficulty learning. Researchers from John Hopkins and National Institutes of Health (NIH) attempted to find a way to reverse the learning disabilities associated with this disorder. They discovered that a single dose of a compound was effective in mouse models.

For this study, the researchers genetically modified mice to have similar characteristics to humans with Down syndrome. The modification in the rats involved giving them extra copies of at least half of the genes on chromosome 21. The characteristics included smaller cerebellums, learning complications and difficulty remembering how to get around a familiar space. Based on previous experiments, the researchers knew that the sonic hedgehog pathway agonist was tied to brain growth and development. For this experiment, the researchers injected a compound right after birth into this particular pathway in the mice. The researchers found that the Down syndrome-like mice experienced significant growth in their cerebellums.

"Most people with Down syndrome have a cerebellum that's about 60 percent of the normal size," said Roger Reeves, Ph.D., a professor in the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins University School of Medicine. "We treated the Down syndrome-like mice with a compound we thought might normalize the cerebellum's growth, and it worked beautifully. What we didn't expect were the effects on learning and memory, which are generally controlled by the hippocampus, not the cerebellum."

The single-dose treatment was effective in reversing some of the learning deficits of Down syndrome. However, the researchers were unable to determine how the dosage worked to reduce the learning disabilities. They plan on doing more research on this process, but in the meantime, the dosage has not been deemed safe at all for humans. The study was published in Science Translational Medicine

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