Mechanism helps protect brain from 
oxygen-deprivation damage

Irvine, Calif., September 13, 2000 — A receptor in the brain protects nerve cells from damage caused by strokes, Alzheimer's disease and other disorders involving the degeneration of nerve cells, a UC Irvine College of Medicine research team has found.

The study, conducted on rats, shows for the first time that the receptor helps the brain prevent injuries caused by stroke; these injuries have eluded treatment for decades. If the findings are confirmed in humans, they could be used to develop more effective treatments for stroke, Alzheimer's disease, Huntington's disease and other nervous system disorders. The researcher's findings appear in the September 2000 issue of Neuroscience.

Dr. Andrius Baskys, assistant professor of psychiatry at UCI and at the Long Beach Veterans Affairs Medical Center, led the team which found that a receptor in the brains of rats called "mGluR" appears to protect the brain against damage when stimulated by moderate amounts of the neurotransmitter glutamate. The same mGluR receptor protects the brain even when much higher levels of glutamate trigger brain damage, sidestep mGluR and stimulate other groups of receptors located in the same area of the brain.

The mGluR receptor prevented damage that would usually be caused by the secretion of very high amounts of glutamate. Excess glutamate production is triggered by oxygen deprivation in the brain. The high levels of glutamate begin cellular processes that kill nerve cells, resulting in stroke and other disorders.

"This is one step closer to unraveling the mystery of why moderate amounts of glutamate seem to protect the brain against damage caused by stroke and other diseases, when those injuries also produce excessive amounts of the same neurotransmitter," Baskys said. "If our findings prove true in humans, they may provide a way to develop better drugs to prevent the cell damage caused by stroke, Alzheimer's, Huntington's disease and other neurodegenerative disorders."

Baskys, who began his work at the University of Toronto, and his team found that if they first injected chemicals that stimulated moderate glutamate levels and later induced the rats to produce high levels of glutamate, the rats did not have the nerve damage normally caused by oxygen deprivation and excess glutamate production.

The team isolated four types of receptors in an area of the brain known as the hippocampus, which is responsible for managing memory. Of these four receptors, the team found that one, the mGluR receptor, operated independently of the other three and was activated only by moderate amounts of glutamate. This receptor triggered different pathways in the cell that ultimately protected nerve cells from damage brought about by overstimulating the other three types of receptors with high levels of glutamate.

Oxygen-deprived nerve cells produce high levels of glutamate, which stimulate a receptor called an NMDA receptor, known for its ability to cause cell death. The mGluR receptor did not bind to NMDA.

"Scientists have long been studying the roles played by glutamate and NMDA in causing nerve cell death after injury," Baskys said. "This study is the first to show that the mGluR receptor and perhaps others like it may offset the injuries caused by the stimulation of NMDA by glutamate. If we target the actions of these receptors, we may be able to eventually develop drugs that can reduce the extensive cell death caused by excess glutamate production."

Baskys and his team at UCI and the Long Beach VA Medical Center are now looking at how the mGluR receptor and other receptors regulate brain cell's susceptibility to injury, and how much glutamate is necessary to trigger the protective effects without producing cell death.

Baskys worked with Yana Adamchick at the University of Toronto, Ontario, on this study.

Contact
Andrew Porterfield
(949) 824-3969
amporter@uci.edu

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