Blocked Neurotransmitter Triggers Epilepsy in Rats

Investigators working with rats have found that blocking transport of gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the central nervous system, caused the animals to develop epilepsy, a disease characterized by rapid and uncontrolled ‘firing' of brain cells. This study was published in the August 1, 2002, issue of the Journal of Neuroscience.

An antisense treatment to reduce expression of the glutamate transporter EAAC1 was used to inhibit movement of GABA into nerve cells. The rats could not synthesize new GABA, so over the course of 10 days, their GABA levels dropped and epileptic symptoms, including staring-freezing episodes and electrographic (EEG) seizures, became apparent. Interfering with other glutamate transporters (called GLAST-1 and GLT-1) found in other types of neurons did not reduce GABA levels or cause epilepsy.

"We have shown that the synthesis and release of GABA depends heavily on transporting glutamate into nerve cells,” said Dr. Jeffrey Rothstein, professor of neurology and neuroscience at Johns Hopkins University (Baltimore, MD, USA; www.jhu.edu) and one of the investigators. "Previously, only glutamate made inside the cell, rather than brought into it, was thought to contribute to GABA manufacture. Getting more glutamate into GABA-producing neurons may help calm the excessive electrical firing of brain cells.”



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