Down syndrome is the most common type of birth defect in children. Its clinical features are mental retardation, backward physical development, special face, and other problems. Although it has long been known that this disease is caused by a chromosomal abnormality (an extra chromosome 21), until now scientists still do not know how this extra chromosome caused such a wide range of effects. In a new study published this week in the Proceedings of the American Academy of Sciences (PNAS), neurologist Anita Bhattacharyya from the Waisman Center at the University of Wisconsin reported that the brain was cultivated using skin cells from individuals with Down syndrome cell.
"Although Down syndrome is very common, it is surprising that we know very little about the error mechanism in the brain. These new cells provide a way for us to observe early brain development," Bhattacharyya said. At the beginning of the study, the Bhattacharyya laboratory transformed the skin from patients with Down syndrome into induced pluripotent stem cells. He then collaborated with Professor Su-Chun Zhang and Jason Weick to continue to cultivate these stem cells into brain cells that can be studied in the laboratory.
One of the important findings they obtained was that they confirmed that the connections between neurons were reduced. Bhattacharyya said: "There is less communication and quieter. This is a new study found, but it is consistent with our only understanding of the Down syndrome brain. Brain cells are known as sudden The connection of synapses communicates, and the number of synapses and synaptic activity of Down syndrome neurons only reach about 60% of the usual. This is enough to make a difference. Even if they later restore these synapses, they missed the key to early development "The window of time." The researchers tested the affected genes in Down syndrome stem cells and neurons and found that the gene on chromosome 21 was increased by 150%, consistent with the genetic contribution of the extra chromosome.
In addition, the expression of about 1500 genes in the genome is strongly affected. "It's not surprising to see changes, but these genes that have changed are surprising," Bhattacharyya. The researchers found that gene expression in response to oxidative stress was significantly increased, which usually occurs when oxygen free radicals damage various tissues.
Bhattacharyya said: "We have confirmed exactly that there is a high level of oxidative stress in Down's syndrome neurons. Other previous studies have also shown this phenomenon and we are happy to find more relevant evidence. Now we have Developed an operating system to study the effects of oxidative stress and how it might be prevented. "
Bhattacharyya said that a series of symptoms of Down syndrome, including accelerated aging, may be caused by oxidative stress. "When people with Down syndrome are 40 years old, they will age very quickly. Their hair will suddenly become gray; the skin develops wrinkles, and many organs also quickly age, showing the appearance of Alzheimer's disease. These Many of the processes may be caused by increased oxidative stress, but this still requires direct testing to verify. "Oxidative stress may be particularly important because it begins to emerge from stem cells. "This indicates that these cells have to spend their entire lives under oxidative stress, which may contribute to the subsequent death of neurons or increase the susceptibility to Alzheimer's disease."
Bhattacharyya said: "We reported this synaptic defect for the first time and reported the effect on genes on other chromosomes in neurons. We are also the first to use stem cells from the same person with or without additional chromosomes. This allows us to observe the differences caused only by extra chromosomes, and exclude the influence of genetic differences between people. "This study is a fundamental exploration of the roots of Down syndrome. Bhattacharyya said that although she hasn't planned to discuss treatment in the short term, they may use these cells to test or intelligently design drugs that target Down's syndrome symptoms.
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