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Prenatal Treatment Cuts Learning Deficits in Mice With Down Syndrome

Mice that have a condition similar to Down syndrome performed better on memory and learning tasks as adults if they were treated before birth with something called neuroprotective peptides, new research from the National Institutes of Health shows.

The researchers studied growth factors that are important at key stages of brain development in the womb. Peptides, small fragments of protein, improve brain cells' ability to receive and send signals and enable them to survive.

People who have Down syndrome have an extra copy of chromosome 21. The Centers for Disease Control and Prevention estimates that about 1 in 691 babies is born with Down syndrome.

In the study, published Nov. 30 in the online journal PLOS ONE, the mice had an extra copy of mouse chromosome 16, which has mouse counterparts to 55 percent of the genes on human chromosome 21.

The researchers treated pregnant mice with peptides for five days, then tested the mouse offspring when they were 8 months to 12 months old, comparing them to mice not treated with peptides. Pregnant mice received injections of the protein fragments beginning eight days after conception—the equivalent of the end of the first trimester in human pregnancies.

Mice with the extra chromosomal material treated with the peptides in the womb learned as well as mice that did not have the extra chromosome, and much faster than mice with the extra chromosome that weren't treated.

To test their learning ability, when the mice reached adulthood, they were placed in a tank of water on a clear platform. The tank had symbols on each wall the mice could use to orient themselves. Researchers placed the mice directly in the water and timed how long it took them to locate the platform. With repeated trials, the mice become more adept at the task and took less time to reach the platform.

Over five days of testing, researchers found that the time the mice spent searching for the platform dropped significantly except for the mice with the extra chromosome not treated in the womb.

"Our study has provided important information that may help in the understanding of Down syndrome," said the study's senior author,Dr. Catherine Y. Spong, chief of the unit on perinatal and developmental neurobiology at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md., where the research was conducted, in a press release.

Her team's research is part of an NIH-wide focus on Down syndrome outlined in 2007. In an earlier study, Spong and her colleagues found that, if treated with neuroprotective peptides in the womb, mice with the extra copy of chromosome 16 achieved developmental milestones earlier than mice with the same condition that were not treated. In that study, researchers examined developmental milestones for sensory, motor skill, and muscle tone development in the first three weeks of life.

"In our earlier work, we showed that treating the mice during pregnancy could prevent developmental delay as assessed with milestones," Dr. Spong said. "In this study, we showed that treatment with [the peptides] not only puts the animals on a typical developmental trajectory, it also improves their ability to learn."

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