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14 October 2010

Enzyme-blocker boosts memory in old mice

Elderly mice with memories addled by age could remember as well as their younger counterparts after receiving a drug that blocks a brain enzyme. The finding could one day help people with memory-impairment.
"It shows that normal memory loss through ageing is not irreversible as many people assume," says Jonathan Seckl of the University of Edinburgh, UK, who carried out the study.
A brain enzyme found in humans and mice, called 11-beta-hydroxysteroid dehydrogenase type 1 (HSD1), amplifies the effects of stress hormones called glucocorticoids in the brain. Over a person's lifetime, this amplification impairs the ability of the hippocampus to store and recover memories, so older people have more trouble with their memory, says Seckl.
Now Seckl and colleagues have shown that this memory-impairment can be reversed by blocking HSD1, at least in mice.

-Testing maze
Seckl gave old mice the drug UE1961 for 10 days, and then gave them a standard memory tests using a maze. He found that the treated mice performed as well as young mice, and better than old mice who had not received the drug.
The drug works by blocking HSD1. "We've shown that relatively short-term inhibition of the enzyme restores memory," says Seckl.
In earlier experiments on mice, Seckl and his colleagues created mice lacking either one or both copies of the gene for making HSD1. They found that the mice lacking the enzyme had no impairment in memory throughout their lives, while ageing mice with only one copy retained their memories much better than ageing mice with two copies.
Seckl now hopes to test the drug in people after toxicology studies have been completed. He is hopeful the drug will work because in 2004, he and his colleagues saw memory recovery in 10 elderly men after he had given them a liquorice extract called carbenoxolone. This also inhibits HSD1, but, as it also inhibits other enzymes, it has side effects including raised blood pressure. The new drug only inhibits HSD1, so Seckl hopes there will be fewer side effects.

**Published in "New Scientist"

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