Scientists improve memory in mice by turning off enzyme

Wednesday, August 28th 2002, 12:00 am
By: News On 6

Scientists have boosted learning and memory in mice by blocking a brain enzyme, and they say the result could point to therapy for reducing forgetfulness in older people.

They said the work implicates the enzyme, called PP1, as a key actor in the brain's system for erasing memories.

Other scientists said it's unclear if the findings may lead to memory-enhancing therapies for older people, but they called the work important.

``This is going to make us think in new and different ways about forgetting,'' said James McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California, Irvine.

``It says here we have a molecule in the brain that is constantly making us forget, and when you block that, it slows down the forgetting.''

The research is reported in Thursday's issue of the journal Nature by a team led by Isabelle Mansuy of the Swiss Federal Institute of Technology in Zurich, Switzerland.

The enzyme was thought to play some role in erasing memories, but its precise job wasn't clear, she said.

The researchers genetically modified mice so they could block PP1 simply by giving the animals food laced with a particular drug.

They found that mice in which PP1 was inhibited did better on learning and memory tests than other mice did. The animals were tested on whether they remembered seeing particular objects and whether they could recall the location of an escape platform submerged in a tank of opaque water.

Aged mice also did better when PP1 was suppressed, hinting at a possible approach to treating age-related memory loss, Mansuy said.

``This indicates that in the aged brain the molecular machinery is not completely deteriorated and that these functions can be restored if only one component _ PP1 _ is blocked,'' she said.

Dr. Eric Kandel, a Columbia University professor who shared the 2000 Nobel Prize for medicine for his work on the nature of learning and memory, said the research is an important step in science's understanding of the brain's constraints on long-term memory formation.

``This shows that if you remove these constraints you enhance the memory storage,'' he said. ``The fact that this is also operative in older mice of course only enhances this work.''

In a second Nature study bearing on brain biology, researchers in Scotland presented evidence that a gene variant linked to Alzheimer's disease might also impair mental abilities in people without the illness. Some prior studies had already suggested that.

They studied 466 people who'd taken a mental ability test at age 11 and again at age 80. Of the group, 121 carried the APOE E4 gene variant, which raises the risk of getting Alzheimer's.

Nobody in the new study had Alzheimer's or any other dementia. But while the test scores of the gene carriers and non-carriers were about the same at age 11, the average scores of the carriers were slightly lower at age 80.