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Bigger Brain, Less Nitric Oxide?

Controlling vital gas may regulate brain size, suggest lab tests

TUESDAY, Nov. 20, 2001 (HealthDayNews) -- Nitric oxide, the molecule behind many of our bodily functions, may also be critical to brain development.

Scientists at the Cold Spring Harbor Laboratory in New York have discovered that altering levels of nitric oxide in the developing brains of tadpoles greatly affects brain size and the number of brain cells. When levels of nitric oxide are lowered, the brains of the animals were much larger and contained more brain cells. If the size difference turns out to be a good thing in future experiments, nitric oxide one day might be a powerful tool against diseases that attack the aging brain, the researchers say.

"We already had the really strong feeling this would be the case," says lead study author Grigori Enikolopov. "We were surprised by the extent to which it happened. We have proven that nitric oxide is an important regulator that the brain uses to control itself."

But the researchers don't know yet if bigger is better, in tadpoles.

"We can't tell if more quantity meant they were smarter or better. There are no tests for that for frogs. At this point, we cannot tell what happened in terms of their behavior," Enikolopov says.

However, preliminary experiments with baby and adult mice show the same results, and mice can be tested for mental acuity, he says.

The findings appear in the Nov. 15 issue of the Journal of Neuroscience.

"I think it's very provocative," says Dr. David S. Bredt, a neurobiologist who specializes in nitric oxide. "I think it's potentially very important. Nitric oxide is one of the major regulators in the body."

Until recently, nitric oxide was credited mostly with regulating blood pressure, although it also plays a part in the body's immune system and nerve responses, Enikolopov says. Nitroglycerin taken by heart patients for chest pain releases nitric oxide into the bloodstream so vessels and arteries relax and widen. And Viagra, that wonder drug used by millions of men to combat impotence, prolongs the effect of nitric oxide in the body so that more blood flows to the penis.

Scientists first discovered that nitric oxide abruptly stopped cell division in a lab dish about 10 years ago, Enikolopov says. Since then, his team has tested the gas on fruit flies cells with the same startling results, leading to the latest study of nitric oxide's role in brain growth.

"We were interested whether a similar function is used by the brain while it grows," Enikolopov says. That would allow stem cells to stop dividing and developing into neurons, or brain cells.

The team used a polymer impregnated with a compound that either encouraged the release of more nitric oxide or discouraged it. Using microsurgery, they injected the polymer into the part of the tadpoles' brains where new cells are produced, which also happened to be where the scientists found the greatest concentrations of nitric oxide.

Without exception, they found that if nitric oxide levels were decreased, the tadpoles' brains were much larger and had more neurons, he says.

"We increased the size of the brain simply by blocking nitric oxide activity," he says.

Bredt says because nitric oxide is a gas, it can reach more cells than the usual chemical neurotransmitters which neurons use to communicate with each other. "It can penetrate through cells and tissue. It can influence a large volume of cells," he says.

Much further down the road, Enikolopov says nitric oxide could be tested on human cells in the lab, and one day the treatment might help reverse the degenerative effects of strokes, Parkinson's disease and Alzheimer's disease.

What To Do:

This article in the Journal of Neuroscience has more about the delicate role of nitric oxide in the brain. For more on the medical uses of nitric oxide, go to the Nitric Oxide Society.

SOURCES: Interviews with Grigori Enikolopov, researcher, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.; David S. Bredt, M.D., Ph.D., associate professor, physiology, University of California at San Francisco; Nov. 15, 2001, Journal of Neuroscience
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