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:10/29/2015)... 2015 NXTD ) ("NXT-ID" ... on the growing mobile commerce market and creator ... a leading marketplace to discover and buy innovative ... wallet on StackSocial for this holiday season.   ... "Company"), a biometric authentication company focused on the ...
(Date:10/27/2015)... 27, 2015 In the present market scenario, ... for various industry verticals such as banking, healthcare, defense, ... growing demand for secure & simplified access control and ... as hacking of bank accounts, misuse of users, , ... as PC,s, laptops, and smartphones are expected to provide ...
(Date:10/27/2015)... , Oct. 27, 2015 Synaptics Inc. (NASDAQ: ... today announced that Google has adopted the Synaptics ® ... controller solutions to power its newest flagship smartphones, the ... Huawei. --> --> ... Google to provide strategic collaboration in the joint development ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... LOS ANGELES and HOLLISTON, Mass. ... Regenerative Technology, Inc. (Nasdaq: HART ), a biotechnology ... announced that CEO Jim McGorry will present ... Tuesday, December 1, 2015 at 2:30 p.m. PT. The ... (link below) for 30 days. Management will also be ...
(Date:11/25/2015)... Oregon , November 25, 2015 ... Market Research Report is a professional and in-depth ... industry.      (Logo: ) ... overview of the industry including definitions, classifications, applications ... is provided for the international markets including development ...
(Date:11/24/2015)... Nov. 24, 2015 Halozyme Therapeutics, Inc. (NASDAQ: HALO ... New York on Wednesday, December 2 at ... , president and CEO, will provide a corporate overview. ... at 1:00 p.m. ET/10:00 a.m. PT . ... will provide a corporate overview. --> th Annual ...
(Date:11/24/2015)... -- Clintrax Global, Inc., a worldwide provider of clinical research services headquartered ... the company has set a new quarterly earnings record in Q3 ... posted for Q3 of 2014 to Q3 of 2015.   ... , with the establishment of an Asia-Pacific ... United Kingdom and Mexico , with ...
Breaking Biology Technology: