May 28, 2013
Stem Cells Help Explore Brain Development In Down Syndrome Patients
Brett Smith for redOrbit.com - Your Universe Online
By reengineering skin cells from individuals with Down syndrome, scientists at the University of Wisconsin, Madison were able to learn how stem cells develop into dysfunctional brain cells when they contain an extra copy of chromosome 21, the genetic cause of the disorder.
"Even though Down syndrome is very common, it's surprising how little we know about what goes wrong in the brain," said Anita Bhattacharyya, a stem cell researcher and co-author of a paper based on the research that appeared in the Proceedings of the National Academy of Sciences.
"These new cells provide a way to look at early brain development,” she added.
The Wisconsin researchers began by transforming two Down syndrome patients´ skin cells into induced pluripotent stem cells, which can then be converted into brain cells.
Bhattacharyya said she noticed something unique about the neurons as they were developing.
"They communicate less, are quieter,” she said. “This is new, but it fits with what little we know about the Down syndrome brain."
The team found that developing neurons in the study had only about 60 percent of the usual number of synapses compared to healthy brain cells. Synapses are the junctures where nerve cells connect with each other and which allow for communication via the transmission of electrical signals.
"This is enough to make a difference," Bhattacharyya said. "Even if they recovered these synapses later on, you have missed this critical window of time during early development."
When looking at the genetic activity in the developing cells, the scientists discovered that genes on the extra chromosome 21 were 150 percent more active, yet consistent with the input of an extra chromosome.
However, Bhattacharyya and her colleagues noticed a higher output from 1,500 genes elsewhere in the genome. These genes are responsible for reacting to the oxidative stress that occurs when molecular fragments called free radicals harm cells.
"It's not surprising to see changes, but the genes that changed were surprising," she said. "We definitely found a high level of oxidative stress in the Down syndrome neurons.”
"This has been suggested before from other studies, but we were pleased to find more evidence for that,” she continued. “We now have a system we can manipulate to study the effects of oxidative stress and possibly prevent them."
Bhattacharyya believes that this genetic activity could explain one of the symptoms of Down syndrome — accelerated aging.
"In their 40s, Down syndrome individuals age very quickly,” she said. “They suddenly get gray hair; their skin wrinkles, there is rapid aging in many organs, and a quick appearance of Alzheimer's disease. Many of these processes may be due to increased oxidative stress, but it remains to be directly tested."
Bhattacharyya suggested that the evidence of oxidative stress could be especially important because it occurs right from the start in the stem cells.
"This suggests that these cells go through their whole life with oxidative stress," Bhattacharyya said. "And that might contribute to the death of neurons later on, or increase susceptibility to Alzheimer's."
The scientist concluded by noting that, "we could potentially use these cells to test or intelligently design drugs to target symptoms of Down syndrome."