Super-smart mice may lead us out of old-age maze

WASHINGTON - Genetic engineering has produced a strain of super-smart mice and may point to a way to help patients with Alzheimer's, mental retardation and perhaps even the annoying "senior moments" that come with ageing, researchers say.

The protein GAP-43, has long been associated with learning. Mice given extra boosts of the GAP-43 gene did much better in mazes used to test rodent intelligence, Aryeh Routtenberg and his colleagues at Northwestern University have found.

What they do not have, Routtenberg stresses, is a smart pill. "Is this a smart drug? Of course it's a gene, so you can't take it," he said.

But he thinks it may be possible to manipulate brain cells so that they produce more GAP-43 when necessary.

"The important point here is that we have the first good evidence that this protein actually regulates learning," said Routtenberg, who reported his findings in the Proceedings of the National Academy of Sciences.

He said GAP-43 was found early in the development of all animals, when neurons were deciding where and how to grow. It was found in high concentrations in one-day-old mice and the combination of stimulation - such as exploring a new environment - and having high levels of the protein helped an animal to learn.

"It maintains the juvenile character ... the childlike appreciation of things," he said.

"It's the same molecule in rodents, monkeys and in man," he said. "It looks like it is regulated in more or less the same way."

Routtenberg's team used mice genetically engineered to produce extra levels of GAP-43.

A Swiss team created the mice, using the GAP-43 gene and a related piece of DNA called a promoter.

The mice were much quicker to learn than wild mice. But the gene had to work just right. Tweaking it to produce a slight mutation ruined the effect.

"The protein by itself is not active unless it has phosphate group on it," Routtenberg said. The process of adding a phosphate molecule, called phosphorylation, is the key to activating many genes.

If researchers could find a way to phosphorylate GAP-43 in humans, it might be a way to help learning without resorting to genetic engineering, he said.

Years of research were needed, but Routtenberg said something as simple as salad oil, with its content of fatty acids such as linoleic and oleic acid, might do the trick.

"We injected olive oil into the brains of rats and found we could facilitate GAP-43 phosphorylation,"

Strains of mice exist that are naturally more intelligent, and Routtenberg found those mice had high levels of GAP-43.

He said he would oppose moves to create a designer drug for people who wanted to be smarter, or who wanted their children to have an advantage in school.

"But I think that we are moving ever closer to finding an agent that will facilitate when we are learning."

- REUTERS

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