Navigation Links
Down syndrome neurons grown from stem cells show signature problems
Date:5/27/2013

Madison, Wis. Down syndrome, the most common genetic form of intellectual disability, results from an extra copy of one chromosome. Although people with Down syndrome experience intellectual difficulties and other problems, scientists have had trouble identifying why that extra chromosome causes such widespread effects.

In new research published this week, Anita Bhattacharyya, a neuroscientist at the Waisman Center at the University of Wisconsin-Madison, reports on brain cells that were grown from skin cells of individuals with Down syndrome.

"Even though Down syndrome is very common, it's surprising how little we know about what goes wrong in the brain," says Bhattacharyya. "These new cells provide a way to look at early brain development."

The study began when those skin cells were transformed into induced pluripotent stem cells, which can be grown into any type of specialized cell. Bhattacharyya's lab, working with Su-Chun Zhang and Jason Weick, then grew those stem cells into brain cells that could be studied in the lab.

One significant finding was a reduction in connections among the neurons, Bhattacharyya says. "They communicate less, are quieter. This is new, but it fits with what little we know about the Down syndrome brain." Brain cells communicate through connections called synapses, and the Down neurons had only about 60 percent of the usual number of synapses and synaptic activity. "This is enough to make a difference," says Bhattacharyya. "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 syndrome stem cells and neurons, and found that genes on the extra chromosome were increased 150 percent, 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," says 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.

"We definitely found a high level of oxidative stress in the Down syndrome neurons," says 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 syndrome includes a range of symptoms that could result from oxidative stress, Bhattacharyya says, including accelerated aging. "In their 40s, Down syndrome individuals age very quickly. 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."

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," Bhattacharyya adds, "and that might contribute to the death of neurons later on, or increase susceptibility to Alzheimer's."

Other researchers have created neurons with Down syndrome from induced pluripotent stem cells, Bhattacharyya notes. "However, we are the first to report this synaptic deficit, and to report the effects on genes on other chromosomes in neurons. We are also the first to use stem cells from the same person that either had or lacked the extra chromosome. This allowed us to look at the difference just caused by extra chromosome, not due to the genetic difference among people."

The research, published the week of May 27 in the Proceedings of the National Academy of Sciences, was a basic exploration of the roots of Down syndrome. Bhattacharyya says that while she did not intend to explore treatments in the short term, "we could potentially use these cells to test or intelligently design drugs to target symptoms of Down syndrome."


'/>"/>

Contact: Anita Bhattacharyya
bhattacharyy@waisman.wisc.edu
608-265-6142
University of Wisconsin-Madison
Source:Eurekalert

Related biology news :

1. Mutation causing wrong-way plumbing explains 1 type of blue-baby syndrome
2. Study examines effects of genetic variants for infants with neonatal abstinence syndrome
3. Grape intake may protect against metabolic syndrome-related organ damage
4. New therapy for fragile X chromosome syndrome discovered
5. Pig wasting syndrome costing farmers millions
6. Found a genetic mutation causing mental retardation very similar to Angelman syndrome in Amish
7. NIH awards nearly $2 million to 3 NYC institutions for chronic fatigue syndrome research
8. Researchers id queens, mysterious disease syndrome as key factors in bee colony deaths
9. Study reveals significance of second trimester markers for Downs syndrome
10. UCI study reveals why Down syndrome boosts susceptibility to other conditions
11. Study offers insights into role of muscle weakness in Down syndrome
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/11/2017)... 2017 Research and Markets has announced the ... to their offering. ... eye tracking market to grow at a CAGR of 30.37% during ... Market 2017-2021, has been prepared based on an in-depth market analysis ... and its growth prospects over the coming years. The report also ...
(Date:4/5/2017)... -- The Allen Institute for Cell Science today announces the ... and dynamic digital window into the human cell. The ... of deep learning to create predictive models of cell ... growing suite of powerful tools. The Allen Cell Explorer ... available resources created and shared by the Allen Institute ...
(Date:4/3/2017)... , April 3, 2017  Data captured ... engineering platform, detected a statistically significant association ... prior to treatment and objective response of ... potential to predict whether cancer patients will ... treatment, as well as to improve both pre-infusion ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... 11, 2017 , ... ComplianceOnline’s Medical Device Summit is back for its 4th ... in San Francisco, CA. The Summit brings together current and former FDA office bearers, ... and government officials from around the world to address key issues in device compliance, ...
(Date:10/11/2017)... ... October 11, 2017 , ... ... implantation and pregnancy rates in frozen and fresh in vitro fertilization (IVF) ... and maternal age to IVF success. , After comparing the results from the ...
(Date:10/10/2017)... ... 10, 2017 , ... Dr. Bob Harman, founder and CEO of VetStem ... The event entitled “Stem Cells and Their Regenerative Powers,” was held ... Harman, DVM, MPVM was joined by two human doctors: Peter B. Hanson, M.D., Chief ...
(Date:10/9/2017)... 9, 2017  BioTech Holdings announced today identification ... its ProCell stem cell therapy prevents limb loss ... Company, demonstrated that treatment with ProCell resulted in ... as compared to standard bone marrow stem cell ... in reduction of therapeutic effect.  ...
Breaking Biology Technology: