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Discoveries in neuroscience

PROVIDENCE, R.I. -- Brown University researchers have discovered that mefloquine, an anti-malarial drug, blocks two gap junction proteins, or connexins, in low doses and with very few side effects in the brains of laboratory mice. The work opens an important door: Connexins found in high concentrations in the brain are believed to play a critical role in movement, vision and memory.

To understand how these communication "tunnels" work, scientists must be able to shut them off. Once those tunnels are disabled, researchers can pinpoint the information that connexins pass between nerve cells and determine how that information affects how the body's development and function.

A technique already exists to study connexins.

Scientists can remove, or "knock out," genes that hold the recipe for connexins, then study the results in mice. But the Brown University scientists who worked on the experiment Barry Connors, professor of neuroscience, and Scott Cruikshank, research associate said "knockout mice" aren't a perfect model. As mice and humans grow, they can compensate for missing genes by turning other genes on or off and cooking up other protein recipes. These biochemical changes can make it difficult to recognize connexins' role.

But mefloquine in adult mice precisely and potently blocks connexins called Cx36 and Cx50. There are about 20 kinds of connexins in the brain and eye, as well in organs such as the heart, liver and pancreas. Cx36 is found in the brain; Cx50 is located in the lens. By specifically blocking them, Cruikshank said mefloquine will be a useful tool for electrical synapse study.

"Mefloquine isn't a magic bullet, but it seems to be better than anything out there," he said. "It's a lot more selective, so it has real utility for science."

Connors said the discovery, detailed in the online early edition of the Proceedings of the National Academy of Sciences for the week of August 2, could shed light on
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Contact: Wendy Lawton
Wendy_Lawton@brown.edu
401-863-1862
Brown University
6-Aug-2004


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