In an article in the Nov. 1 issue of The Journal of Clinical Investigation, the Rochester scientists describe a new mechanism by which brain cells can be damaged during chronic neurodegenerative diseases. When inflammation occurs in the brain, nerve impulses that are passed between cells during routine activities like learning and memory can become toxic. Instead of triggering the formation of memories, these impulses can inflict injury on neurons and disrupt neurologic function.

Understanding this mechanism could provide a new path for drugs to treat the diseases. Working in collaboration with researchers at the University of California at San Diego, the Rochester scientists propose a strategy of chemical preconditioning to induce adaptations in nerve cells that would enable the cells to better withstand toxic attacks, prevent injury, and preserve function.

"Preconditioning would allow the nervous system to experience stress and become more resistant to future encounters with stress and the damage it can trigger," said Harris A. Gelbard, M.D., professor of Neurology at the University of Rochester Medical Center and the research project's principal investigator.

A long-standing villain in neurodegenerative disease has been glutamate, an amino acid that normally acts as a neurotransmitter. Excess glutamate, however, can overly excite neurons, causing damage and death a process called excitotoxicity. Some drugs developed for the treatment of Alzheimer's disease, for example, are designed to lower the production of glutamate or block its transmission to reduce excitotoxic injury.

"But just blocking glutamate doesn't seem to work efficiently in neurodegenerative diseases with inflammation," said Gelbard. "We reconsidered how excitotoxi
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Contact: Michael Wentzel
michael_wentzel@urmc.rochester.edu
585-275-1309
University of Rochester Medical Center
3-Nov-2005