Researchers in the US analysing brain cells grown from skin cells of people with Down’s syndrome have made discoveries that could shed more light on the condition, including why they tend to age more quickly than the general population.
The study by neuroscientists at the Waisman Center at the University of Wisconsin-Madison, published in the Proceedings of the National Academy of Sciences journal, also made discoveries about brain activity in people with Down’s syndrome.
"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 neuroscientist at the Waisman Center. "These new cells provide a way to look at early brain development."
Reduction in brain cell connections
One significant finding was a reduction in connections among brain cells. Brain cells communicate through connections called synapses, and the Down’s neurons had only about 60% of the usual number of synapses and synaptic activity.
"They communicate less, are quieter,” said Bhattacharyya. “This is new, but it fits with what little we know about the Down’s syndrome brain. This is enough to make a difference. Even if they recovered these synapses later on, you have missed this critical window of time during early development."
The researchers looked at genes that were affected in the Down’s syndrome stem cells and neurons, and found that genes on the extra chromosome were increased 150%, consistent with the contribution of the extra chromosome.
However, the output of about 1,500 genes elsewhere in the genome was strongly affected. "It's not surprising to see changes, but the genes that changed were surprising," said Bhattacharyya. The predominant increase was seen in genes that respond to oxidative stress, which occurs when molecular fragments called free radicals damage a wide variety of tissues.
Preventing oxidative stress
"We definitely found a high level of oxidative stress in the Down’s syndrome neurons," said Bhattacharyya. "This has been suggested before from other studies, but we were pleased to find more evidence for that. We now have a system we can manipulate to study the effects of oxidative stress and possibly prevent them."
Down’s syndrome includes a range of symptoms that could result from oxidative stress, including accelerated aging, said Bhattacharyya. "In their 40s, Down’s syndrome individuals age very quickly. They suddenly get grey 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."
Oxidative stress could be especially significant, because it appears right from the start in the stem cells. "This suggests that these cells go through their whole life with oxidative stress, and that might contribute to the death of neurons later on, or increase susceptibility to Alzheimer's."