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Iron Deficiency Causes Misfiring of Brain Signals

Iron Deficiency Causes Misfiring of Brain Signals


The urges to move and the unpleasant leg sensations in people with restless legs syndrome are caused by low iron levels and mixed nerve signals, according to a new study.

Last year, Pennsylvania State University researchers found that iron deficiency in certain areas of the brain was linked to restless legs syndrome.

Now, experts from Penn State and Johns Hopkins University have new insight on how iron deficiency affects the brain and prompts restless legs syndrome.

Restless legs syndrome affects an estimated 5%-10% of the U.S. population, according to a Penn State news release. Symptoms include irresistible urges to move the legs and arms and "creepy-crawly" sensations in the limbs. The symptoms worsen during periods of rest or while sitting or lying down, particularly in the evening and at nighttime. It can lead to difficultly falling asleep, daytime sleepiness, and fatigue.

In 2003, Penn State researchers investigating restless legs syndrome found that a part of the brain in people with restless legs syndrome wasn't getting enough iron. These people lacked portals called transferrin receptors that let iron enter brain cells.

Now, Penn State's Xinsheng Wang, MD, PhD, and colleagues know more about the consequences of that iron deficiency.

Studying lab rats and donated human brain cells from autopsies, the researchers found that the same area revs up the production of an enzyme called tyrosine hydroxylase (TH) when they have low iron levels.

TH, in turn, regulates the production of a brain chemical called dopamine, which helps transmit the brain's messages to the legs, creating body movements.

You might think that would help the brain get its messages out to the rest of the body.

However, dopamine requires iron as well as TH. Without enough iron, the "recipe" is incomplete. As a result, the brain's signals to the body are scrambled, and the misfiring causes restless legs syndrome.

It's too early to know if iron supplements might help alleviate restless legs syndrome.

The researchers plan to look into that possibility; meanwhile, it's best to check with your health-care provider before tinkering with your iron intake, since getting too much iron can cause other health issues.

Another possibility to control restless legs syndrome might be using drugs to replace dopamine in the brain, which could temporarily normalize nerve signals sent out by the brain. Researchers are also investigating steps to normalize iron levels in the brain of people with restless legs syndrome.

"Our next steps are to continue investigations of treatment strategies for restless leg syndrome involving iron supplementation and dopamine agents to attempt to reach the normal balance between iron and dopamine in the brain," says Penn State neurosurgery professor James Connor, PhD, in a news release.

Connor, the vice chairman of Penn State's neurosurgery department, worked on the current and 2003 studies of restless legs syndrome and iron.

The new findings were presented in San Diego at Neuroscience 2004, a meeting of the Society for Neuroscience.

SOURCES: Neuroscience 2004, San Diego, Oct. 23-27, 2004. News release, Pennsylvania State University. WebMD Medical News: "Cause Found for Restless Leg Syndrome."

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