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Chemical Improves Older Monkeys' Visual Ability
Ageing is inevitable for all living things, so it is understandably tempting for humans to seek drugs or treatment to postpone it. Apart from alchemists who tried to make immortality pills, serious scientists have also been working on this issue for rather a long time.

A team of neuroscientists from the United States and China last month reported an advance in this field.

The researchers applied tiny amounts of a chemical known as gama-aminobutyric acid (GABA) to neurons in the brains of old monkeys. They found that the treatment restored the neurons' ability to distinguish the orientation of lines and the direction of moving objects, renewing long-lost powers of discrimination.

This finding, which was published in the scientific journal Science last month, refreshed people's understanding of GABA, a brain-calming neurotransmitter that has been used to reduce feelings of anger and anxiety.

Julie Mendelson, a neuroscientist at the University of Toronto in Canada, was quoted as saying: "Anything that can show a reversal in the effects of ageing is really exciting and potentially beneficial."

She and many others are optimistic that this kind of research will eventually lead to drugs that will improve the lives of older people. However, others cautioned that the finding, though exciting, applies only under very strict conditions.

The research targets a major aspect of ageing, namely the degradation of visual functions during old age, according to Zhou Yifeng, a member of the research team and a fellow from the University of Science and Technology of China.

Elderly people often find that their vision is no longer as sharp as it was when they were young. They often respond slowly in visual tests, Zhou said.

He noted that many of these sensory problems suffered by the elderly stem not from deterioration of the eyes but from a decline in the region of the brain that processes visual information, known as area V1.

Tests on a macaque monkey's neurons in the V1 area found it responded selectively to lines oriented at a particular angle and to bars moving in a particular direction.

But in 2000, Audie Leventhal -- of the University of Utah School of Medicine in Salt Lake City -- and his co-workers reported that V1 neurons in very old monkeys lose much of this selectivity.

Their finding caught the attention of the National Institute of Health of United States. The institute decided to fund the research in the hope that a new treatment may be developed to restore the old monkeys' visual selectivity.

Zhou said: "They believe that discovering ways to restore the visual function of the old monkeys may be of greater significance than the finding itself." As Leventhal's student in the early 1990s, Zhou first got involved in the research two years ago.

Leventhal and Zhou were later joined by three others from China and the United States. In the new study, they tried to reverse the age-related decline in monkeys aged between 26 and 32, equivalent to between 78 and 96 years in human terms.

They studied a total of 242 neurons in six young monkeys aged between 7 and 9, the equivalent of young humans aged between 21 and 27. They also studied 257 neurons in seven old monkeys aged between 26 and 32.

The monkeys' responses to a range of orientations and directions were carefully recorded.

Then the researchers applied GABA to the inhibitory neurotransmitter in the elderly monkeys' brains and tried a GABA-like drug called muscimol on their V1 area.

The scientists discovered that the proportion of the old monkeys' brain cells for selecting a particular orientation nearly doubled and that direction-selective cells roughly tripled, approximating the proportions found in monkeys aged 7 to 9 years old.

"That is to say, the neurons resumed their ability to process the visual information as they did in the younger monkeys," Zhou said.

The scientists also observed that the two chemicals had no effect on the selectivity of V1 neurons in the younger monkeys.

Leventhal suggested that GABA-dependent neural communication declines with age and that this decline is to blame for old monkeys' indiscriminate neurons.

Indeed, when the team blocked GABA in younger animals, those animals' neurons lost their orientation and direction selectivity, in effect ageing them 20 years in an instant.

Zhou said the number of the neurons tested guaranteed the reliability of the experiment.

"It is not like having one or two samples to get the result," he noted.

Yet one query still remains unanswered: Why does GABA communication decline with age?

One possible answer was suggested by Ulf Eysel of the Ruhr University Bochum in Germany. He said some evidence hints that the inhibitory cells that use GABA are particularly sensitive to disruptions of blood flow to the brain.

Over time, these effects may kill cells or reduce their ability to make and release GABA.

Another finding was that GABA improved the cortical neurons' ability to discern visual stimuli from the background, another indication that the neurons can regain activity.

Previous research on GABA has found a similar decline in GABA-supported networks in the ageing auditory system. As in visual areas, these networks are important for helping the brain extract information from a noisy environment.

Their deterioration could explain age-related trouble following a conversation at a loud party or navigating through traffic.

The researchers have already envisioned a drug that restores lost GABA functions in the appropriate brain regions.

While exciting in itself, the finding may not lead to any drug soon, Zhou cautioned.

Although the experiment found that some of the V1 cells in the old monkeys demonstrated responses typical of cells in young monkeys after the application of the drug, most cells exhibited only a partial recovery as a result of the GABA application.

This suggested that factors other than a degradation of the GABA communication may be involved in the decline in the cortical cells.

Zhou said more tests still need to be done to see if the treatment would have any side effects on human health.

Another Chinese neuroscientist who was asked to comment on the finding cautioned that Leventhal and his colleagues did the experiment on anaesthetized monkeys.

"Their response may differ from that of the animal in a normal state," he said, declining to be identified.

Even if a drug based on GABA was successfully created to improve the visual function of the elderly, it may not necessarily be the solution to ageing.

The human body is like a car, the Chinese scientist said. When it gets old, this is not because merely one single part of it gets old.

"You cannot make it into a new one by changing the tyres alone," he said.

Even so, a new tyre is better than an old one, he conceded.

(China Daily June 27, 2003)

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