Stanford University scientists have found a novel way to hone in on brain defects associated with autism. The researchers have taken skin cells from humans with Timothy syndrome who also have autism, potentially discovering how to block abnormal brain signals associated with autism spectrum disorder.
For the study, the scientists used an elaborate process to grow brainlike spheres from skin cells.
Postdoctoral scholar Sergiu Pasca, MD, and Ricardo Dolmetsch, PhD, associate professor of neurobiology led the study.
People with Timothy syndrome were used because they are thought to have a gene mutation that makes calcium channels defective in the brain’s neurons.
The researchers explain it’s been difficult to study brain and nervous system disorders like autism because researchers can’t study living brain cell samples from humans.
For their study they used induced pluripotent stem cells, or iPS cells.
"We developed a way of taking skin cells from humans with Timothy syndrome and converting them into stem cells, then converting those stem cells into neurons," said Dolmetsch.
The scientists grew free-floating iPS cells in cells in a nutrient-rich solution, and then transferred the clumps to tissue culture plates where they formed three layers which approximated living tissue in the human brain.
The cells taken from Timothy syndrome patients with autism had higher spikes in calcium levels that interfered with communication between cells. The calcium spikes suggested the neurons can’t shut themselves off.
Spikes in calcium brain signaling also caused changes in the way genes were expressed.
The cells grown from skin taken from Timothy patients also showed changes that suggest neurons in the right and left hemispheres of the brain don’t connect, found in past studies.
An even more significant finding was that the neurons grown from Timothy syndrome cells made g too much of an enzyme that is crucial for producing dopamine and norepinephrine, both of which are essential for sensory processing and social behavior
Dolmetsch says this is the first time scientists have been able to study living human cells to find clues to autism. "These results could lead to a very powerful research tool," he said. "It's human psychiatric disease in a petri dish."
The finding that calcium channel defect was the culprit in producing too much dopamine and norepinephrine means it may be possible to treat autism by reversing the abnormality. The study is published in the journal Nature Medicine.
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