|
Thinking may harm people with chronic brain diseases
BY JAMIE TALAN
STAFF WRITER
February 2, 2006, 8:43 PM EST
The process of thinking may actually be harmful to people with chronic brain diseases such as HIV dementia and Alzheimer's.
Scientists at the University of Rochester Medical Center have discovered a rather alarming mechanism: The inflammation triggered by these conditions turns normal nerve impulses -- neurons talking to one another -- into a toxic language that can damage cells outright.
Dr. Harris A. Gelbard, a professor of neurology and principal investigator of the study published recently in the Journal of Clinical Investigation, has been researching the brain circuitry that goes awry in these mind-robbing conditions.
While colleagues in the neuroscience field have focused on the death of the neuron itself, Gelbard followed the destruction occurring beforehand when two cells were trying to talk to one another.
Gelbard and Matt Bellizzi witnessed under a microscope disturbing behavior in dendrites, the branchlike part of the neuron that conducts impulses from the body of the cell to another cell. Dendrites have spines sprouting out like twigs, and at the end of the curved branch is a synapse, a chemical handshake with the neighboring cell. Cells need the synapse to communicate.
Gelbard and Bellizzi saw that the dendrites growing in the damaged brain were beading -- creating a foxhole and disappearing. The synapse couldn't function properly. Then -- surprise -- the beading stopped and the dendrite's disappearing act was over. The synapse was also restored.
Gelbard and his colleagues realized that the beading -- the disappearing act -- was associated with functional deficits in the cell. When inflammation wasn't present, normal cell-to-cell communication flowed.
This dendritic beading has also been observed in the brains of animals with Alzheimer's. AIDS brains had the same beading. When nerves tried to communicate during a learning experience, the inflammation triggered this beading and prevented information from getting from one cell to the next. Abnormal amounts of calcium were also produced.
"This is an exceedingly innovative discovery," said Dr. Howard Gendelman, chairman of experimental neuroscience at the University of Nebraska. "This work brings us a significant step forward in developing new ways to detect and treat brain diseases."
Once Gelbard realized that inflammation was at the heart of this process, he began testing drugs to quiet this abnormal immune response.
"We got the idea to use a drug that buffers calcium and reduces inflammation," said Gelbard.
And it worked. Pretreating with a medicine normally used in emergency rooms to treat severe hypertension, Gelbard found that it prevented beading.
"It saved the synapse," he said. "It has to get to the right place and in the right dose, but you can do almost anything to neurons and they won't die."
He believes that this approach, conditioning neurons to withstand stress, could be used in early stages of dementia to strengthen vulnerable cells.
The National Institute of Mental Health is testing a variety of compounds to treat AIDS dementia. One class of drugs being studied is the anti-epileptic medicines that appear to have anti-inflammatory properties. Clinical trials are under way. Gelbard's work was funded by the same agency.
|