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Neurons grown from skin cells may hold clues to autism
Date:11/27/2011

entering cells, causing a tell-tale set of abnormalities throughout the body. Proper functioning of the calcium channel is known to be particularly critical for proper heart rhythm many patients die in childhood of arrhythmias but its role in brain cells was less well understood.

To learn more, Dolmetsch and colleagues used a new technology called induced pluripotent stem cells (iPSCs). They first converted skin cells from Timothy Syndrome patients into stem cells and then coaxed these to differentiate into neurons.

"Remarkable reproducibility" observed across multiple iPSC lines and individuals confirmed that the technique can reveal defects in neuronal differentiation such as whether cells assume the correct identity as the brain gets wired-up in early development, said the researchers. Compared to those from controls, fewer neurons from Timothy Syndrome patients became neurons of the lower layers of the cortex and more became upper layer neurons. The lower layer cells that remained were more likely to be the kind that project to areas below the cortex. In contrast, there were fewer-than-normal neurons equipped to form a structure, called the corpus callosum, which makes possible communications between the left and right hemispheres.

Many of these defects were also seen in parallel studies of mice with the same genetic mutation found in Timothy syndrome patients. This supports the link between the mutation and the developmental abnormalities.

Several genes previously implicated in autism were among hundreds found to be expressed abnormally in Timothy Syndrome neurons. Excess cellular calcium levels also caused an overproduction of neurons that make key chemical messengers. Timothy Syndrome neurons secreted 3.5 times more norepinephrine and 2.3 times more dopamine than control neurons. Addition of a drug that blocks the calcium channel reversed the abnormalities in cultured neurons, reducing the proportion of catecholam
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
Source:Eurekalert  

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