Tuesday, 28 May 2013

Stem cells give insight into Down's syndrome

Down syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of an extra chromosome. Despite being the most common chromosome abnormality in humans, scientists have yet to unveil why an extra chromosome causes so many symptoms and widespread effects. Now, a new study by researchers at the Waisman Centre, University of Wisconsin-Madison gives new insight in the underlying causes of the syndrome.

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

The scientists began their study by turning skin cells, harvested  from two patients with Down Syndrome,  into induced pluripotent stem cells (iPSCs). Then, Bhattacharyya and her colleagues induced these stem cells to become brain cells.

Further investigation revealed that people with Down syndrome have "quieter" brain cells, meaning that their brain cells have fewer synapses. A synapse is a structure that permits a neuron (or nerve cell) to communicate with another cell by passing an electrical or chemical signal through it. Down neurons have only 60 % of the number of synapses and synaptic activity healthy people have.

Structure of a typical chemical synapse
Structure of a typical chemical synapse

"They communicate less, are quieter. This is new, but it fits with what little we know about the Down syndrome brain. Even if they recovered these synapses later on, you have missed this critical window of time during early development." said Bhattacharyya

The research team looked at genes that were affected both in the stem cells and the derived neurons and discovered that gene activity on the extra chromosome, chromosome 21, wa greatly increased - by 150 % percent- especially on the genes that respond to damage from free radicals, which are believed to play a role in ageing.

"It's not surprising to see changes, but the genes that changed were surprising. 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" said Bhattacharyya

Bhattacharyya explains that the Down syndrome comes with a range of symptoms that could result from oxidative stress, like accelerated ageing. Individuals with Down syndrome are known to gain grey hair, wrinkles and even the appearance of someone with Alzheimer's disease quite early in their lives.

"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." said Bhattacharyya.

Finally, Bhattacharyya mentioned that although other researchers have already created Down syndrome neurons from iPSCs, she and her team are the first to report a synaptic deficit in patients with Down syndrome.

"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."

Down syndrome (DS) is the most common chromosome abnormality in humans. It is typically associated with a delay in cognitive ability (mental retardation) and physical growth, and a particular set of facial characteristics.The average IQ of young individuals with DS syndrome is around 50, whereas young adults without the condition typically have an IQ of 100.

Video on Down Syndrome

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