Study on world's oldest monkeys may explain age-related mental decline
May 5, 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."
American Association for the Advancement of Science
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