frogs and understanding neurological disorders

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Frog science helps to explain how the environment may have permanent

effects on the nervous system

Published: Wednesday, 11-Aug-2004 News-Medical.Net

Scientists studying how the nervous system develops in frogs have found

that altering the pattern of electrical signaling in individual neurons

changes the kinds of neurotransmitters they produce.

While preliminary, the finding may lead to a new understanding of how

epilepsy and other neurological disorders develop and may even point to

new ways of preventing or treating these disorders.

Many neurological and mental disorders result from problems with

neurotransmitters (nerve-signaling chemicals). Some of these chemicals,

called excitatory neurotransmitters, increase the amount of activity in

the nervous system, while others, called inhibitory neurotransmitters,

decrease the amount of activity. Previous studies have shown that

environmental signals can cause some neurons to change the

neurotransmitters they express, but researchers thought this phenomenon

was restricted to just a few kinds of neurons under limited

circumstances. The new study shows that the phenomenon is widespread, at

least in frogs, and that factors influencing electrical activity in

individual neurons can play a role in fine-tuning the functions of many

neurons in the nervous system. The study was funded in part by the

National Institute of Neurological Disorders and Stroke (NINDS) and

appears in the June 3, 2004, issue of Nature.1

" The data suggest that the type of neurotransmitter produced results

from a partnership between genetic regulation and electrical activity, "

says senior author C. Spitzer, Ph.D., of the University of

California, San Diego. " This allows more flexibility than genes alone,

but it is a two-edged sword - the system can also be perturbed more

easily. If we can turn the edges of the sword to our advantage, we may

be able to help the nervous system heal itself. "

The researchers studied the developing spinal cord in frog embryos. In

one set of embryos, they genetically manipulated properties of the cell

membranes in order to increase or decrease the neurons' electrical

activity. In other embryos, they did the same thing using drugs.

Increasing the amount of electrical activity in the neurons increased

the number that produced inhibitory neurotransmitters, the researchers

found. Lowering the amount of activity in the neurons increased the

production of excitatory neurotransmitters. In both cases, the changes

seemed to be an attempt by the nervous system to regain a balance

between excitatory and inhibitory signals.

By looking at cells in a culture dish, the researchers found that

increasing or decreasing electrical activity for as little as 5 hours

was enough to cause the changes they observed. Altering the neurons'

activity later did not reverse the effect. This suggests that there are

critical periods for these changes during development, the researchers

say.

Usually when the nervous system adapts to drugs or other stimuli, it

does so by changing the neurotransmitter receptors on nerve cells, says

le Leblanc, Ph.D., a program director at NINDS. This study shows

that neurons also can change the neurotransmitters themselves. " It helps

to explain how the environment may have permanent effects on the nervous

system, " Dr. Leblanc says. This information might help researchers

understand how epilepsy, depression, and other disorders develop. It may

also lead to new understanding about how drugs used to treat

neurological disorders might cause long-term changes in the nervous

system, she adds.

While the results are intriguing, this study looked only at how spinal

cord signaling develops in embryonic frogs. The researchers don't know

yet if similar changes might be at work in the brain, or whether they

occur in adult animals and/or in humans. More studies are needed to

answer these questions.

If researchers can learn how to control the neurotransmitter changes in

people, they might be able to find better treatments for human diseases,

Dr. Spitzer says. " If we understand how the car works, then we can fix

it. "

Dr. Spitzer and his colleagues are now planning follow-up studies to

identify the mechanisms that cause the nervous system to regain

equilibrium. It may be necessary to control these mechanisms in order

for therapies that alter neuronal activity to be effective. They are

also planning studies to see if other kinds of neurotransmitters are

regulated in the same way as the ones examined in this study.

The NINDS is a component of the National Institutes of Health within the

Department of Health and Human Services and is the nation's primary

supporter of biomedical research on the brain and nervous system.

http://www.ninds.nih.gov/