Navigation Links
Down syndrome neurons grown from stem cells show signature problems

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
University of Wisconsin-Madison

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:
(Date:10/27/2015)... YORK , Oct. 27, 2015 In ... major issues of concern for various industry verticals such ... is due to the growing demand for secure & ... in various ,sectors, such as hacking of bank accounts, ... for electronic equipment such as PC,s, laptops, and smartphones ...
(Date:10/26/2015)... LAS VEGAS , Oct. 26, 2015 /PRNewswire/ ... innovator in modern authentication and a founding member of ... of its latest version of the Nok Nok™ S3 ... use standards-based authentication that supports existing and emerging methods ... is ideal for organizations deploying customer-facing applications that require ...
(Date:10/22/2015)... 2015  Aware, Inc. (NASDAQ: AWRE ), a leading supplier ... third quarter ended September 30, 2015.  --> ... was $4.0 million, a decrease of 33% compared to $6.0 million ... quarter of 2015 was $2.2 million, or $0.10 per diluted share, ... the same period a year ago.  --> ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... 2015 --> ... "Oligonucleotide Synthesis Market by Product & Services (Primer, Probe, ... DNA, RNAi), End-User (Research, Pharmaceutical & Biotech, Diagnostic Labs) ... market is expected to reach USD 1,918.6 Million by ... CAGR of 10.1% during the forecast period. ...
(Date:11/24/2015)... LEXINGTON, Massachusetts , November 24, 2015 ... Officer, will participate in the Piper Jaffray 27 th Annual ... on Tuesday, December 1, 2015, at 8:30 a.m. EST (1:30 p.m. ... Poulton , Chief Financial Officer, will participate in the Piper Jaffray ... City , NY on Tuesday, December 1, 2015, at 8:30 ...
(Date:11/24/2015)... Nov. 24, 2015 /PRNewswire/ - Aeterna Zentaris Inc. ... that the remaining 11,000 post-share consolidation (or 1,100,000 ... (the "Series B Warrants") subject to the previously ... November 23, 2015, which will result in the ... effect to the issuance of such shares, there ...
(Date:11/24/2015)... , ... November 24, 2015 , ... InSphero AG, the ... cell culture models, has promoted Melanie Aregger to serve as Chief Operating Officer. ... served on the management team and was promoted to Head of InSphero ...
Breaking Biology Technology: