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Brain receptor linked to epilepsy

11 June, 2001

Research linking the neurotransmitter GABA with the development of epilepsy have been reported in the journal Molecular and Cellular Neuroscience.

The neurones that make up the circuitry of the brain must constantly co-ordinate and interpret the millions of signals they both receive and send out. These signals are carried by chemical messengers called neurotransmitters which can be classified as either excitatory 'go' or inhibitory 'stop' molecules. If the relative levels of these competing signals develop an imbalance, messages can become 'scrambled' and conditions, such as epilepsy, can develop.

Despite the vast complexity of the brain circuitry, two simple neurotransmitters, GABA (gamma-aminobutyric acid) and glutamate, orchestrate the majority of the brain's opposing signals. In basic terms, GABA means 'stop' and glutamate means 'go'. GABA is the major calming influence within the brain and works by binding to, and activating, specific receptors on nerve cells. One of the key receptors in this process is the GABAB receptor, which comprises two subunits - GABAB1 and GABAB2. However, the importance of each of these subunits in determining the functional roles of GABAB receptors has remained controversial.

"This is a significant advance in our understanding of information transfer in the brain, and it points towards new investigational approaches for creating better treatments", said Frank Walsh, senior vice president, GlaxoSmithKline (GSK). Dr. Walsh heads GSK's Centre of Excellence for Drug Discovery - Neurology.

In this study researchers at GSK report how specially bred mice lacking only the GABAB1 subunit are completely unable to transmit any GABAB receptor-mediated signals. Furthermore, the deficit in these animals leads to the development of severe epilepsy within a few weeks of birth. This condition is characterised by spasm and convulsive movements and is strikingly similar to human tonic-clonic seizures. This finding provides vital evidence that GABAB1 is essential for all GABAB signalling in the brain and that its function cannot be substituted for by a back-up protein. More importantly, they show that GABAB signalling is involved in the prevention of epilepsy.