Neuron research may hold hope for Alzheimer's
Last Updated: Thursday, July 8, 2010 | 12:29 PM ET
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U.S. scientists have found a chemical that can form neurons in brains of mice, and improve the memory of old rats.
The results, to be published in the journal Cell on Thursday, offer hope for a cure "that will address the core illness process in Alzheimer's disease," said Dr.Thomas Insel, director of the U.S. National Institute of Mental Health (NIMH).
The researchers found a chemical they called P7C3, which supported the formation of neurons — a process called neurogenesis — in the dentate gyrus region of the brain in mice.
But most new neurons do not survive the month between their creation and becoming a useful part of the brain. Such neurons "fare much worse in aging-related disorders like Alzheimer's, marked by runaway cell death," NIMH said in a news release.
The work, led by Steven McKnight and Andrew Pieper, both of University of Texas Southwestern Medical Center in Dallas, showed P7C3 increased the production of neurons and gave them a better chance of getting wired into the brain.
Over three years, the team they led checked 1,000 molecules to see if any of them could boost production of neurons in the adult mouse hippocampus, where the dentate gyrus is located.
P7C3 protected the new neurons.
They then tried the chemical on mice that lacked a gene so they were almost completely incapable of producing new neurons. Humans without this gene have learning disabilities, and mice without the gene also have abnormalities.
"These mice are bad at making new neurons," McKnight said. "The question was: Can you fix that? And the answer to that was yes." With the P7C3, the normal function of the hippocampus returned.
Next came experiments on rats, because the mice they had been using could not swim, and a swimming test is a key indicator of memory function in rats.
"Aged rats normally show a decline in neurogenesis associated with an inability to form new memories and learn tasks," Pieper said.
But prolonged treatment with P7C3 increased both the birth and survival of new neurons, and the rats' memories and ability to learn. They showed significant improvements in their ability to swim to the location of a hidden platform, and when the platform was removed, still swam to the same place. The platform experiment is a standardized test of learning and memory in rats.
The researchers actually found eight chemicals of the 1,000 they tested with the potential to aid neuron growth and survival, but focused on P7C3 because of its other properties.
"It can be taken orally, crosses the blood-brain barrier with long-lasting effects, and is safely tolerated by mice during many stages of development," McKnight said.
McKnight, chairman of biochemistry at UT Southwestern, and Pieper, an assistant professor of psychiatry and biochemistry, started their research to find out if there was a way of strengthening the process by which mammals' brains add new neurons into adulthood.
"Our chances were slim," Pieper said.
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