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Press Images
Rhesus monkeys like those used in a University of Utah study
of age-related decline in brain-cell function include 4-year-old
Ding-Ding (A), 7-year-old Miki (B), 14-year-old Yi-Yi [C]
and 26-year-old Grandpa Solomon (D). Other monkeys were
used in the study. Those pictured live in China.
To
download high-resolution click here:
Credit: Kunming Institute of Zoology, China.
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Background
Aging in humans is known to reduce visual acuity, depth perception
and the abilities to distinguish colors, contrasts and shapes.
The new study builds upon research Leventhal published in 2000
in the journal Nature Neuroscience. That study found that
when vision declines in elderly monkeys, it is not necessarily
because of diseases of the eyes or optic nerves, but because of
age-related degeneration in nerve cells within the brain's visual
cortex.
In that study, Leventhal measured electrical activity of individual
nerve cells in the brain as young and old monkeys watched a computer
screen that alternately displayed vertical bars, horizontal bars
and angled bars that moved at different speeds and directions.
In young monkeys, horizontal bars triggered certain nerve cells
to fire, vertical bars made other neurons fire and angled bars
triggered still others. Yet other neurons fired to help the young
monkeys determine directions of moving objects. Such firing of
distinct nerve cells helps young monkeys distinguish different
orientations and motions in what they see.
But in older monkeys, various nerve cells fired regardless of
whether the bars were vertical, horizontal, angled or moving in
various directions. The findings suggested that when elderly drivers
have trouble determining directions and speeds of other vehicles,
it might be due to degradation of brain cells that help them distinguish
shapes and motions. The 2000 study suggested driver's license
eyesight tests for elderly people fail to detect brain degeneration
that impairs vision.
The Science study
The new study in Science was carried out in a similar manner.
Leventhal and colleagues measured electrical activity in 242 visual
cortex nerve cells in six young monkeys ages 7 to 9 years old
- equivalent to 21- to 27-year-old humans. They measured activity
in another 257 nerve cells in seven old monkeys 26 to 32 years
in age - equal to 78 to 96 in humans. Rhesus monkeys and long-tailed
macaques were involved in the study.
As in the previous study, monkeys in the new experiment watched
computer screens displaying bars at various orientations and moving
at different speeds and directions. This time, however, Leventhal
and colleagues also administered drugs to the animals, including:
-- GABA (gamma-aminobutyric acid), which is the major "inhibitory
neurotransmitter" found throughout the brain. It acts like
a traffic light to regulate the flow of nerve impulses and squelch
random and excessive nerve cell firing.
-- Muscimol (pronounced musk-keh-mole), which works like GABA
but is more potent and is extracted from poisonous, psychoactive
Amanita mushrooms.
-- Bicuculline (pronounced buy-kook-you-lean), which acts to counter
GABA and muscimol, by elevating random nerve impulse activity.
When GABA and muscimol were used, they did not improve the already
good function of nerve cells in young monkeys' brains. But within
two minutes, the drugs made old monkeys' visual cortex nerve cells
act "young" again. Instead of various cells firing regardless
of whether monkeys saw vertical, horizontal or angled bars, some
cells fired only when the monkeys saw vertical bars, some fired
only when horizontal bars were seen, and so on. This ability to
discriminate shapes and motions wore off five to 10 minutes after
the drugs were stopped.
When bicuculline was used on young monkeys, their brain cells
temporarily acted "old" by firing indiscriminately in
response to the various bar shapes and motions.
"You make cells young or old depending on what drug you're
using," Leventhal says.
GABA and muscimol had another beneficial effect. As we age, there
is more background "noise" - random nerve impulses in
the visual cortex - so when an older person sees something, the
resulting nerve signals are harder to detect against the background
noise. Yet when old monkeys received GABA or muscimol, "it
squelched this random background activity," adding to the
improved function of the monkey's visual cortex.
While Leventhal's 2000 study and most of the new one were conducted
in Utah, many future studies will be done at China's Kunming Institute
of Zoology because it is less expensive and the animals are available
in the area's temperate rainforest.
Traffic lights in the brain
GABA helps regulate timely and efficient flow of nerve signals
by acting like traffic lights, Leventhal says. During a blackout,
signals fail and traffic crawls to a standstill. If GABA is reduced,
nerve impulses move less efficiently and a person's memory, motor
coordination, hearing and vision are impaired, he adds.
Leventhal says that while much modern medical research aims to
regenerate injured or lost body parts - such as repairing spinal
cord cells damaged by injury or disease - he wants to get our
existing brain cells to keep working well as we age.
"It would be nice to fix paralysis to have nerve cells grow
back, but as far as your brains and your brain cells, you need
to have the same ones last forever, because they hold our memories
and knowledge so new ones will no longer be you."
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