MOLECULE MAY BE IMPORTANT PART OF BRAIN'S ELECTRIC TOOLBOX

November 17, 1994
Media Contact:Gary Stephenson
Phone: (410) 955-5384
E-mail: Gstephen@welchlink.welch.jhu.edu

Studies by scientists at The Johns Hopkins Medical Institutions suggest that the brain uses a common chemical to adjust the speed and intensity of the messages carried through its circuits.

Researchers showed that adding a phosphate molecule to brain cells can make it easier for messages to go through.

The demonstration provides important insight into the tools the brain uses to create learning and memory. The same tools may also play a role in brain damage from strokes and other disorders.

"If the link between phosphorylation and learning bears out, we might one day be able to improve memory and learning by carefully adjusting the body's ability to use phosphorylation on nerve cells," says Richard Huganir, Ph.D., associate professor of neuroscience and an associate investigator at Howard Hughes Molecular Genetics Institute.

"But we also have to proceed with care, because too much phosphorylatioa could overexcite a nerve cell and kill it by letting too much calcium into the cell," he says.

Huganir studied phosphate molecules' effects on certain receptors, sites on nerve cells that open in response to chemical messengers from other nerve cells. While the receptors are open, calcium and sodium from around the nerve cell flow into it, triggering a series of electrical and chemical chain-reactions that transmit the message up the nerve cell.

"A single receptor that we studied probably has 10 to 20 different sites where this phosphate molecule can be added, and each of these sites has different effects on the receptor," explains Huganir.

"At one site we looked at, phosphorylation increases the amount of time the receptor is open," says Huganir. "Another affects the concentration of receptors, causing more to gather in a particular area."

When a receptor is open longer or more receptors are gathered together, more of the calcium surrounding the cell flows into it, making the message come through more easily and more strongly.

Similarly, a memory appears to be associated with a series of changed nerve cells that, when prompted, fire more easily or more strongly.

To confirm the link between phosphorylation and memory, Huganir is currently trying to develop a strain of mice where the sites that allow phosphates to bind to receptors are altered or missing.

Receptors can also overexcite and kill nerve cells by letting in too much calcium. Although the theory is still controversial, some doctors have begun to link overexcitation to Alzheimer's and Huntington's disease. More evidence exists associating overexcitation with brain damage from stroke.

Some phosphorylation sites may close receptors; if so, doctors will try to use such sites to prevent nerve-cell death.

Huganir's research was funded by the Hughes Institute. Huganir will present his findings on November 17 at a special symposium, "Structure, Function, and Regulation of Glutamate Receptors," at the annual meeting of the Society for Neuroscience. He is also chair of that symposium. The society's meeting takes place November 13-18 in Miami Beach, Fla.


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