U. may have discovered a brain cell rejuvenator

0 Comments | Deseret News (Salt Lake City), May 1, 2003 | by Joe BaumanDeseret News staff writer

Can medicine rejuvenate aging brain cells? A new scientific study suggests it may be possible someday.

Research by a team of University of Utah and Chinese scientists shows that in rhesus monkeys' visual response dulled by age can be renewed by a drug. What may be most extraordinary about the research to be published in Friday's issue of Science magazine is that the implications are for all sorts of brain function, not just vision.

How well you see depends not only on the physical health of the eyes. Another vital aspect is how the brain handles the electrical impulses streaming in from the eyes via the optic nerve. In elderly monkeys and humans, the visual cortex tends to lose discrimination.

As a University of Utah news release explained it, nerve cells in the brain's visual center eventually seem to become degraded and lose ability to distinguish shapes and motions.

Audie G. Leventhal, an author of the study and professor of neurobiology and anatomy at the U. School of Medicine, told the Deseret News he began wondering what happens in the brain as people and other higher creatures age.

His team began studying the world's oldest monkeys, comparing their visual responses to those of younger simians. "We immediately found that responses of cells in the cerebral cortex got worse" the older the monkeys were, he told the paper.

They had deteriorated in that they had lost their ability to distinguish one type of visual target from another. The nerve cells were responding too strongly, to all sorts of visual stimulation. "The result was, the cells responded . . . to non-selected things."

The background activity in the brain seemed to be triggering responses in older rhesus monkeys. Younger animals are able to filter that out better.

"We developed a means of delivering various drugs to the cerebral cortex," to see what could be done to affect visual perception, he said.

When dosed with a class of neurotransmitter drugs called GABA (gamma-aminobutyric acid), "the cells started responding much as they do with young animals," he said.

When the dosage was discontinued, the elderly monkeys' visual perceptions dropped back.

Oddly, the material that helps elderly monkey brains is not a stimulant but a sort of tranquilizer. At first blush, that seems counterintuitive, because what an older creature might seem to need is an accelerant, not something to slow brain function.

The results say, in effect, "when you're 85, moving really slowly, you need to be inhibited to be moving faster," Leventhal explained.

But on second thought, it makes perfect sense. GABA is an inhibitor, acting as a gate used to slow and control the nerve impulses. "It gets rid of unwanted information," he said.

If cars could drive through Salt Lake City without regulation, traffic would halt in a terrible snarl. Only with stop signs, rules, traffic lights, can vehicles move smoothly. The same is true with brain cells processing visual stimuli. A gate-keeper like GABA acts as a traffic cop.

But the visual cortex isn't the only part of the brain requiring the same kind of regulation. "It's almost certain to be true throughout your whole cerebral cortex," Leventhal said. The cerebral cortex regulates higher functions, like thinking.

Tranquilizers of some types increase GABA levels in the brain. That does not mean old folks should rush out and dose themselves up with tranquilizers. More study is required before any therapy can begin, with side-effects a big unknown.

Another question: How long will it last? The U. noted the researchers were able to reverse age-related deterioration of nerve cells "for several minutes" while GABA was administered.

Leventhal wants to get pharmaceutical companies to research the effects, to discover whether older people could use low doses to improve cognitive function without suffering serious side effects.

Meanwhile, the U. and Leventhal are seeking a patent on the use of GABA and similar drugs to improve brain function in the elderly.

If this turns out to be a viable brain rejuvenator, when could elderly people expect some help?

"A lot of drugs actually are available on the market," said Leventhal's co-author, Yongchang Wang, a research assistant professor of neurobiology and anatomy at the U. "We're thinking in terms of neurotransmitter inhibitor of activities" that might help with rejuvenating brain-power.

"So how do you bring up the neurotransmitter level to the normal? There's many ways to do so. . . . If this (indication) is correct, it can be very soon."

He too is eager for drug companies to expand research and put the idea into clinical trials. The results could be important in several areas, Wang said.

"What else for the motor cortex? What else for other sensory areas?"

Other authors of the study are Mingliang Pu, a former research associate at the University of Utah; Yifeng Zhou, a neurobiologist training in Leventhal's lab, now at the University of Science and Technology of China, Hefei; and Yuanye Ma of the Kunming Institute of Zoology in Kunming, China.