Public Release:  Of mice and memory

In a new USC study, experimental compounds that mimic antioxidants delayed memory loss in mice. Researchers hope the drugs will do the same for humans some day.

University of Southern California

Two synthetic antioxidants that may prove to be more powerful versions of those found in nature reversed age-related memory loss in mice, a University of Southern California study found.

Antioxidants, found in vitamins like A, C and E, are thought to help delay aging and prevent disease.

The experimental compounds were modeled after the enzymes catalase and superoxide dismutase. They both help fight off free radicals - destructive particles that harm cells and lead to wrinkles and the other effects of aging.

"Because enzymes are huge molecules, they can't go through the cell membrane and they provoke an immune response. The body identifies them as foreign molecules and tries to destroy them," said Michel Baudry, the study's lead investigator and a biological sciences professor in the USC College of Letters, Arts & Sciences.

Through the company he co-founded, Eukarion Inc., Baudry developed synthetic versions of the two enzymes that were not only smaller but more effective than typical antioxidants because catalytic activity enabled them to fight more than one free radical.

If the two naturally-occurring enzymes are the body's foot soldiers, Baudry's versions - simply named EUK-189 and EUK-207 - work like a lighter, faster special forces team that can slip inside cells undetected and fight tirelessly.

"When the antioxidant Vitamin E, for example, interacts with a radical, it's a one-shot deal. It can't interact with another radical," Baudry said. "Our molecules are small. They can get through the membranes and interact with more than one molecule of free radicals."

For the study - funded by the National Institute on Aging - Baudry teamed up with Richard Thompson, the Keck Professor of Psychology and Biological Sciences at USC, and a colleague at the University of California, Irvine.

The findings are published in the current print edition of the Proceedings of the National Academy of Sciences.

The researchers implanted 8-month-old mice - the rodent equivalent of middle age - with a time-release pump that contained either of the two experimental compounds. They studied them through their 11th month of life.

Borrowing a page from the famed Russian scientist Ivan Pavlov, they used fear conditioning to test the mices' memory.

The mice were placed in a cage with an electrical grid floor and given a mild shock.

"The next day, we came back and put the animal in the same cage," Baudry said.

"She thinks she's going to get a shock, so she freezes. This is something we call context fear. It shows she remembers. If she doesn't remember, then she's going to move around and not exhibit this freezing behavior."

The mices' biochemistry also was tested so researchers could discern on a cellular level which ones had accumulated the least oxidative damage as a result of the drugs.

Thompson said the mice treated with the experimental compounds fared much better.

"We found that these drugs prevent the age decline in memory," Thompson said. "These may be much more effective than antioxidants in humans."

Baudry said human clinical trials will be the next step.

"These drugs could eventually be adapted to fight almost any disease which has an oxidative component," he said.

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To view the study, go to http://www.pnas.org.

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