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Rice University study finds possible clues to epilepsy, autism
Date:12/9/2008

Rice University researchers have found a potential clue to the roots of epilepsy, autism, schizophrenia and other neurological disorders.

While studying the peripheral nerves of the Drosophila, aka the fruit fly, Rice doctoral student Eric Howlett discovered an unanticipated connection between glutamate an amino acid and neurotransmitter in much of the food we eat and phosphoinositide 3-kinase (PI3K), an enzyme that, Howlett found, regulates the activity of neurons.

Howlett and his colleagues, graduate student Curtis Chun-Jen Lin, research technician William Lavery and Michael Stern, a professor of biochemistry and cell biology, discovered that negative feedback mediated by PI3K regulates the excitability of neurons, an issue in a number of ailments that include neurofibromatosis, and that a mutation in a glutamate receptor gene common to both the fruit fly and humans has the ability to disrupt that regulatory mechanism.

Howlett found the Drosophila's metabotropic glutamate receptor (DmGluRA) gene, when mutated, increased the excitability of the neuron by preventing PI3K from doing its job.

Published online by the Public Library of Science Genetics, the study is the culmination of four years of work that built upon research by Marie-Laure Parmentier and her team at the University of Montpelier, France, to connect glutamate to regulatory functions in the fruit fly.

"As science often goes, we didn't set out with this hypothesis," said Howlett, who began the project on funding obtained by Stern from the Department of Defense to study neurofibromatosis. "This all came about as a control for a completely different experiment, and we said, 'Wow, this is some interesting stuff.'"

What he saw was that the overexpression of PI3K in motor neurons had a dramatic effect. "I noticed under the scope that these nerves were really big, and electrophysiologically, they were really slow. That wasn't what I expecte
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Contact: David Ruth
druth@rice.edu
713-348-6327
Rice University
Source:Eurekalert

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