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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.