Scientists looking to understand the fundamental brain mechanisms of autism spectrum disorder have found that a gene mutation known to be associated with the disorder causes an overstimulation of brain cells far greater than that seen in neuronal cells without the mutation.
The Rutgers-led study, spanning seven years, employed some of the most advanced approaches available in the scientific toolbox, including growing human brain cells from stem cells and transplanting them into mouse brains.
The work illustrates the potential of a new approach to studying brain disorders, scientists said.
Describing the study in the journal, Molecular Psychiatry, researchers reported a mutation — R451C in the gene Neurologin-3, known to cause autism in humans — was found to provoke a higher level of communication among a network of transplanted human brain cells in mouse brains. This overexcitation, quantified in experiments by the scientists, manifests itself as a burst of electrical activity more than double the level seen in brain cells without the mutation.
“We were surprised to find an enhancement, not a deficit,” said Zhiping Pang, an associate professor in the Department of Neuroscience and Cell Biology in the Child Health Institute of New Jersey at Rutgers Robert Wood Johnson Medical School and the senior author on the study. “This gain-of-function in those specific cells, revealed by our study, causes an imbalance among the brain’s neuronal network, disrupting the normal information flow.”
The interconnected mesh of cells that constitutes the human brain contains specialized “excitatory” cells that stimulate electrical activity, balanced by “inhibitory” brain cells that curtail electrical pulses, Pang said. The scientists found the oversized burst of electrical activity caused by the mutation threw the mouse brains out of kilter.
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