The GABA-ergic system in an animal model of temporal lobe epilepsy

Temporal lobe epilepsy is one of the most common but also most serious types of epilepsy. More than one third of the patients suffering from this disease are responding insufficiently or are even resistant to antiepileptic drug treatment. In some instances they can be however cured or at least significantly improved by surgical removal of the epileptic focus. This focus is mostly located in the temporal lobe and they`re in the hippocampus. The hippocampus is a brain area with highly "plastic" properties as seen by rapidly occurring adaptive changes altering the biochemistry and physiology of the neuronal circuitry within the brain area. These mechanisms are crucial for the recruitment of short time memory. They may, however, play a crucial role for the development of epilepsy. Our project was directed on such malfunctioning plastic changes in the course of epileptogenesis in animal models of epilepsy. We focused on the neurotransmitter systems GABA (the major inhibitory neurotransmitter in the brain) and on neuropeptide Y, an also inhibitory neuropeptide often co-stored and co-released with GABA. To our surprise we observed prominent adaptive changes suggesting the development of potent endogenous anticonvulsive mechanisms in the epileptic brain area (the hippocampus) of these animals. Such possible endogenous protective mechanisms include the synthesis of the inhibitory transmitter GABA in otherwise excitatory neurons. This is accompanied by enhanced expression of the inhibitory GABA receptor in the same neurons, making it likely that GABA released from these cells may act on its receptors on the same cell. Also NPY becomes overexpressed in the same neurons and may act on its receptors mediating an inhibition of the release of the excitatory transmitter glutamate. We were able to replicate most of these finding also in specimens from epilepsy patients indicating the relevance of such mechanisms also for epilepsy patients.