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Jun 20, 2007

Researchers Find Role of Autism Proteins

  • Neuroligin-1 and neuroligin-2, two proteins implicated in autism, were found to control the strength and balance of nerve-cell connections, report researchers at University of Texas Southwestern Medical Center.

    The investigators genetically manipulated rat neurons in culture so that the cells created too much neuroligin-1. The cells developed twice the usual number of synapses, raising the question of whether neuroligin-1 contributed to the formation of additional excitory synapses or contributed to the failure of existing ones to be pruned. Similar tests showed that excess neuroligin-2 also led to more synapses, but in this case, the synapses were inhibitory.

    When the cells that overexpressed either neuroligin-1 or neuroligin-2 were chemically prevented from firing, they did not develop excess synapses despite the presence of the respective proteins. Together, the tests indicate that nerve cells with excess neuroligins developed extra synapses only when those cells are allowed to fire.

    Because mutations in neuroligins occur in some people with autism spectrum disorders, the scientists also engineered a mutation in neuroligin-1 comparable to one observed in humans and introduced the mutant neuroligins into rat neurons.

    “The nerve cells carrying the mutant neuroligin showed a dramatic decrease in the number of synapses and a more than twofold decrease in excitability, showing that the mutation interferes with the stability of the synapses,” says Ege Kavalali, Ph.D., associate professor of neuroscience and physiology at UT Southwestern and an author of the paper.

    The study will be published in the June 21 edition of Neuron.



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