May 2, 2003 Scientists may have discovered why the brain’s higher information-processing center slows down in old age, affecting everything from language, to vision, to motor skills. The findings may also point toward drugs for reversing the process.
A brain chemical called GABA helps neurons stay finicky about which signals they respond to – a must for the brain to function at its peak. Certain neurons in very old macaque monkeys lose their pickiness, researchers have found, seemingly because they don’t get enough GABA. These results appear in the journal Science, published by the American Association for the Advancement of Science (AAAS).
If a lack of GABA is indeed responsible for the old neurons’ indiscriminate firing, this problem may be simple enough to treat. Existing drugs, such as Xanax, increase GABA production, according to author Audie Leventhal of the University of Utah School of Medicine. These drugs haven’t been carefully tested on the elderly, though.
"The good news is there are a lot of drugs around that can facilitate GABA-ergic function and maybe some of them will help," said Leventhal.
Leventhal and his colleagues studied visual function in monkeys he believes are the oldest in the world. The monkeys live in a colony in Kunming, China, established as part of a Chinese and Russian experimental program in the 1950s. At 30 years old (around 90 in people years), these animals have lived around twice as long as they do in the wild.
“They really do sort of look like grandpa. They have thinning hair and wrinkles,” Leventhal said.
In monkeys, as well as humans, visual function declines with age. While the eye itself does degenerate, this decline also involves the vision-related section of the cerebral cortex, which is responsible for many “higher-order” brain functions.
What the researchers discovered about the visual system likely applies to age-related declines in other parts of the cerebral cortex, according to Leventhal,
"If it's going on in the visual cortex, it's probably going on in other parts of the cortex," he said.
In the visual cortex, each so-called “V1 neuron” responds only to the sight of objects at a specific orientation or moving in a certain direction. GABA probably restricts the V1 neurons from responding to any other types of stimuli. This process helps the brain make sense out of the vast quantities of visual information coming in through the eyes.
"It’s like New York City or Boston during a blackout,” Leventhal said, describing what would happen if neurons weren’t restricted to specific responses. “With all the gating mechanisms like the stoplights out, you’d think traffic would move faster. But it doesn’t."
The researchers recorded the activity of individual neurons in the visual cortex of old and young macaque monkeys, while showing the monkeys various images on a computer screen. The devices that monitored the neurons also held small glass tubes of substances that could be released directly onto the neurons. The substances were GABA, a GABA-enhancing compound called muscimol, and a GABA-blocking compound called bicuculline.
The GABA blocker made the neurons less selective in the young monkeys, but had no significant effect in old monkeys. Presumably, that’s because the older neurons had already lost much of their selectivity, according to the researchers.
GABA and the GABA-enhancer had a relatively small effect in the young monkeys, moderately increasing the percentage of cells that were selective for particular orientations and directions. In the old monkeys, however, GABA and the GABA-enhancer had a much stronger effect, significantly increasing the percentage of highly selective cells.
Thus, the visual cortex of the older monkeys seemed to function less effectively, because GABA wasn’t limiting the neurons to specific responses. Exactly how this change occurred isn’t completely clear. In their Science paper, the researchers speculate that perhaps GABA production decreases in older brains.
Leventhal is hoping that more researchers will begin study aging in monkeys.
“It’s absolutely remarkable to me that my lab is the only lab in the world studying higher brain function in old monkeys. Old monkeys are rare, but the world is full of old human primates,” Leventhal said. “Hopefully we can drum up a little interest, and encourage other people who are trying to figure out how come their kids are smarter than they are now.”
Leventhal’s co-authors are Youngchang Wang and Mingliang Pu of the University of Utah School of Medicine, in Salt Lake City, UT; Yifeng Zhou of the University of Science and Technology of China, in Hefie, China; and Yuanye Ma of Kunming Institute of Zoology, Chinese Academy of Science, in Kunming, China. The study was supported by the National Institute of Aging, National Institutes of Health.
Founded in 1848, the American Association for the Advancement of Science (AAAS) has worked to advance science for human well-being through its projects, programs, and publications, in the areas of science policy, science education and international scientific cooperation. AAAS and its journal, Science, report nearly 140,000 individual and institutional subscribers, plus 272 affiliated organizations in more than 130 countries, serving a total of 10 million individuals. Thus, AAAS is the world's largest general federation of scientists. Science is an editorially independent, multidisciplinary, peer-reviewed weekly that ranks among the world's most prestigious scientific journals. AAAS administers EurekAlert! (http://www.eurekalert.org), the online news service, featuring the latest discoveries in science and technology.
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