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Lithium chloride slows onset of skeletal muscle disorder
Date:3/18/2008

evels in mice genetically engineered to develop Alzheimer's disease. LaFerla and his research team then wondered: Could lithium chloride also reduce phospho-tau levels and symptoms in mice with IBM?

First, they sought to determine how the inflammation affects the skeletal muscle fibers. They injected the mice with a drug to trigger muscle inflammation, then put them on tiny treadmills to test their motor function. As expected, mice with inflammation could not keep up with the control mice, indicating reduced motor function. Examining their brain tissue, the scientists discovered the mice with muscle inflammation also had higher levels of phospho-tau.

Through additional testing, they discovered an enzyme called GSK-3 beta was responsible for increasing the tau phosphorylation. Previous studies have shown that same enzyme to cause tau buildup in the Alzheimer's brain.

Next, the scientists sought to block the accumulation of phospho-tau in the IBM mice with the goal of curbing motor function loss. In mice six months of age, one group was fed lithium chloride-laced food for six months, and a second group was fed regular food. At 12 months of age, mice in the first group performed on the treadmill as if they were six months of age, while mice in the second group had reduced motor function. Lithium chloride, the scientists found, blocked the GSK-3 beta enzyme that caused higher levels of phospho-tau.

"The older animals were performing as if they were younger animals," said Kitazawa, a postgraduate researcher of neurobiology and behavior at UCI and co-author of the study. "Lithium chloride was delaying their rate of decline."

The scientists then sought evidence that their results in mice might translate to humans with IBM. They performed tests on human muscle tissue samples and found the GSK-3 beta enzyme again played a role in the phosphorylation of tau. That was not the case, though, in patients with other muscle disorders.
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Contact: Jennifer Fitzenberger
jfitzen@uci.edu
949-824-3969
University of California - Irvine
Source:Eurekalert

Page: 1 2 3

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