UNC Findings May Help Explain Cause of Most Common Movement Disorder

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CHAPEL HILL - Scientists at the University of North Carolina at Chapel Hill may have identified the genetic basis underlying essential tremor disease, the most common human movement disorder.

The discovery comes from studies involving a strain of genetically altered mice that show the same types of tremor and similar lack of coordination as people affected by essential tremor.

This animal model of the disease might prove useful for screening potential treatments, said Dr. A. Leslie Morrow, associate director of UNC's Bowles Center for Alcohol Studies and professor of psychiatry and pharmacology in UNC's School of Medicine.

"We believe that these mice could explain one etiology, or origin, of essential tremor disease in humans because of the marked similarities between the mouse model and the human disease," said Morrow, who led the study team.

A report of the findings will appear in the March issue of the Journal of Clinical Investigation.

An estimated 5 million Americans are affected by essential tremor, a neurological disease characterized by an uncontrollable shaking of the limbs, in particular the arms and head. Unlike resting tremor associated with Parkinson's disease, symptoms of essential tremor are noticeable during movement, such as lifting a cup of coffee.

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The causes of essential tremor disease remain unknown, and current therapies are either partially effective or carry undesirable side effects.

The finding is serendipitous, Morrow said, because the study was initiated in an effort to learn more about alcoholism and the tremors that result from alcohol withdrawal. Her group had been examining a unique breed of laboratory mice that has been genetically engineered to lack a molecule called the gamma-aminobutyric acid-A (GABA-A) receptor alpha-1 subunit.

GABA-A receptors reside on the surface of brain cells where they help the brain to relay "stop" messages throughout the body. Two alpha-1 subunits combine with three other proteins to form the most common type of GABA-A receptor, but this subunit is absolutely required for these GABA-A receptors to exist in brain, Morrow said.

The mice lacking alpha-1 subunits have about 50 percent fewer GABA-A receptors in the brain than normal mice. A defect in GABA-A receptor function could contribute to the loss of muscle control that characterizes essential tremor patients, Morrow said.

"There is a reduction of the GABA-A receptor alpha-1 subunit in animal models of alcohol dependence, so we wanted to study the mice. As soon as we obtained them we noticed that they had a tremor."

The symptoms in GABA-A receptor alpha-1 deficient mice had the same properties as those in people who suffer from essential tremor, suggesting to the authors that the mice might respond to drugs used to treat human patients.

"Very low doses of alcohol are effective at ameliorating tremor in human patients. Interestingly, we observed the same effect in these mice

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