Many of you may already know that Down’s syndrome is caused by an extra copy of a single chromosome. Instead of having two copies of chromosome 21, 1 out of every 691 babies are born with three copies. And as you might expect, having thousands of extra genes throwing chaos into the delicate balance of human biochemistry is not a good thing.
However, even though we know the basic underpinnings of the condition, exactly what that extra genetic material does to the brain and body is unknown. After all, cutting into peoples’ brains isn’t exactly a method recognized by most ethical boards as a good way to conduct science.
Scientists are finding ways around this issue, though. For starters, they’ve been creating mice with a similar extra chromosomal copy and cutting into their brains. But there’s a key word in that sentence – similar. Mice don’t have the exact same chromosome 21 as humans. To study the exact molecular mechanisms of Down’s syndrome, researchers have to create the exact system to study.
This is precisely what scientists at the University of Wisconsin have been up to for the past several years. They’ve managed to take skin cells from Down’s syndrome patients and create induced pluripotent stem cells with them. With a bit of nudging, these artificial stem cells can create any type of tissue in the body. For these new studies, scientists had them form neurons in a laboratory setting.
Presto. Instant Down’s Syndrome neurons to study.
By looking at how these neurons grow early on in their development, the researchers were able to draw two possible conclusions about why the additional active genes causes such problems. First, the neural networks had 50 percent fewer synaptic connections than healthy ones. This caused a “quieter” network overall, which fits with what scientists know about the Down’s syndrome brain. The second noticeable difference was the additional output of 1,500 genes elsewhere in the genome outside of chromosome 21, the majority of which respond to oxidative stress.
Perhaps you’ve heard that antioxidants are super healthy for you because they catch “free radicals.” What this means is that the molecules you’re ingesting have room for an extra electron or two. Having extra electron absorbers coursing through your veins means you have less electrons running around knocking structures out of whack, a.k.a. oxidative stress.
In Down’s syndrome patients, having overactive genes that respond to these free radicals running around could accelerate aging. Having electrons destroying biomolecular structures on an increased basis is hardly the way to stay young.
“In their 40s, Down syndrome individuals age very quickly,” said Anita Bhattacharyya, a neuroscientist at the Waisman Center at the University of Wisconsin. “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.”
Will these new insights lead to new treatments for the effects of the debilitating disorder? Only time will tell.
The paper, “Deficits in human trisomy 21 iPSCs and neurons,” was published in the Proceedings of the National Academy of Sciences by Bhattacharyya and 15 colleagues at the University of Wisconsin.