Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Mixed signals to blame for restless legs syndrome


Iron-deficient cells in the brain are mixing up central nervous system signals to the legs and arms causing the irresistible urges to move and creepy-crawly sensations that characterize restless legs syndrome (RLS), a Penn State College of Medicine study reports.

"Our previous studies established a physical cause for RLS showing certain cells in the brain were iron deficient," said James R. Connor, Ph.D., professor and vice chair for neurosurgery, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center. "We have now found a sequence of events that may connect that cellular iron deficiency to the uncontrollable movements of the disorder."

The study was presented today (Oct. 25, 2004) by Xinsheng Wang, M.D., Ph.D., postdoctoral fellow in Connor’s laboratory, at the Society for Neuroscience’s scientific meeting, Neuroscience 2004, held in San Diego. RLS, a syndrome that may affect 5 percent to 10 percent of the U.S. population, causes irresistible urges to move the legs and arms and is often accompanied by creepy-crawly sensations in the limbs. The sensations are only relieved by movement and become worse as the sun goes down, causing night after night of sleeplessness for those with RLS and their partners.

In normal individuals, cells in a portion of the middle brain called the substantia nigra control the production of tyrosine hydroxylase (TH), an enzyme. The cells also determine how much of the TH is phosphorylated, or activated. The active TH regulates the production of dopamine, a substance in the brain that transmits messages from the brain and central nervous system to the body, giving it instructions for normal functioning.

Connor’s team found that people with RLS have very high levels of active TH. Although this should result in more dopamine being made, in fact, the proper regulation of dopamine production is only possible with both active TH and adequate levels of iron. "We think the ’active form’ has lost its feedback mechanism," Connor said. "The cell is getting a signal that more dopamine is needed so TH is made and shifted to the active form, but the activity is compromised because less iron is available. If the iron was present in sufficient amounts, the feedback process would signal the cells to stop or slow TH production."

Connor’s team first made the connection between iron deficiency and elevated TH levels by examining the brains of iron deficient rats. After weaning, the rats were divided into two groups. One group was given a normal diet, and the second, an iron deficient diet. Half of those that were given the iron deficient diet were later put on a normal iron diet. At 65 days, all rats, regardless of diet, had elevated levels of TH drawing the connection between cellular iron deficiency in the brain and elevated TH. However, the TH levels of the rats that had started a normal diet immediately after weaning eventually returned to normal. "This shows us that developmental iron deficiency can be reversed, but that extended iron deficiency cannot be," Connor said. In a second study using a human cell culture model, the research team exposed PC12 cells, which create dopamine, to a substance that removes iron from cells. As more of the substance was added to the cells and, consequently, more iron was removed, the expression of TH grew, connecting the cellular iron deficiency to elevated TH in human cells.

In a third study, brain tissues from eight individuals with RLS were compared to tissues from the brains of five healthy individuals. The brain tissue was acquired through the Restless Legs Syndrome Foundation’s brain collection at the Harvard Brain Bank. As the animal and cell culture models suggested, the autopsy analysis of the brains of those with RLS showed that iron-deficient cells from the middle brain expressed high levels of TH compared to the non-RLS group. "These results continue to support the idea that the brain dopaminergic system is altered in RLS and that the differences in the dopaminergic system are consistent with insufficient iron," Connor said.

These findings explain why some RLS sufferers find relief from taking dopaminergic drugs. Although not FDA-approved for the treatment of RLS, the drugs are used to calm tremors in those with Parkinson’s disease. The dopaminergic agents replace dopamine in the brain and temporarily improve the nerve signal transmission to the body. "Our next steps are to continue investigations of treatment strategies for RLS involving iron supplementation and dopamine agents to attempt to reach the normal balance between iron and dopamine in the brain," Connor said.

In addition to Connor and Wang, other study authors were: John Beard, Ph.D., and Byron Jones, Ph.D., Penn State University; and Christopher J. Earley, M.B., B.Ch., Ph.D., and Richard Allen, Ph.D., Johns Hopkins Bayview Medical Center.

Valerie Gliem | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

For graphite pellets, just add elbow grease

23.03.2018 | Materials Sciences

Unique communication strategy discovered in stem cell pathway controlling plant growth

23.03.2018 | Agricultural and Forestry Science

Sharpening the X-ray view of the nanocosm

23.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>