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Copper circuits help brain function -- could tweaking the circuits make us smarter?

When released into neural synapses, the copper damps down the activity of these antennas, called NMDA receptors. The activity of NMDA receptors determines how strong the connections between nerves cells are and changes in the receptors' activity are critical to cell survival, learning and memory. "In the brain, some neurons have strong connections, and some have weak connections, but this is changing all the time," says Gitlin, who is also director of genetics and genomic medicine at St. Louis Children's Hospital and scientific director of the Children's Discovery Institute. "The plasticity of the connections between neurons is important for nerve cell survival and for our ability to think the way we do. The NMDA receptors are a large component of this process, and we've found that Atp7a and copper are key factors controlling them."

Since the Atp7a protein is responsible for moving copper in nerves, variations in the gene for Atp7a could influence copper flow in the nervous system and the function of NMDA receptors.

The researchers' findings stem from earlier research on the rare neurodegenerative disorder Menkes disease, which results from an abnormal Atp7a gene. The loss of properly functioning Atp7a protein in Menkes patients leads to impairment of copper distribution in the body. Children born with the disease have intractable seizures and mental retardation and seldom live beyond the age of ten.

The current research showed that in mouse nerve cells that lacked Atp7a and so were not able to bring copper to synapses, the resulting high activity of NMDA receptors caused excitotoxic cell death, a process that kills nerve cells that have been overstimulated. This suggests that in the brains of people with Menkes, NMDA receptors, no longer appropriately modulated by copper, may kill important neurons and cause neuronal degeneration. Pharmaceutical companies are working on drugs that inhibit excitotoxic nerve cell death, and Gitlin thinks
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Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University School of Medicine
25-Sep-2006


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