| Temporal lobe epilepsy (TLE) is a disorder characterized by recurrent seizures and anatomical pathology usually in the hippocampus. It is thought that an imbalance between excitation and inhibition in this structure causes or contributes to epileptogenesis. The imbalance is probably due to a number of things including cell loss, mossy fiber sprouting, and potential synaptic and/or receptor dysfunction. Using the pilocarpine rat model of TLE, alterations in GABAergic function of acutely isolated cells in the hippocampus have been demonstrated; DGCs exhibit enhanced GABA efficacy, zinc sensitivity, and clonazepam sensitivity with diminished zolpidem sensitivity while CA1 neurons exhibit decreased GABA efficacy and clonazepam sensitivity. Human TLE patient DGCs exhibit similar GABA{dollar}sb{lcub}rm A{rcub}{dollar} receptor functional alterations. The seemingly silent period of time between the initial insult and the occurrence of spontaneous recurrent seizures also shows functional and pharmacological changes in the GABA receptor, some different from those observed during the chronically epileptic state. In addition, RT-PCR techniques have pointed to decreases in some of the subunit mRNA of the GABA{dollar}sb{lcub}rm A{rcub}{dollar} receptor. Because the subunit composition of the receptor confers its pharmacological and physiological properties, alterations in this composition may account for the functional changes observed. In conclusion, there is an abundance of evidence indicating a possible breakdown in the inhibitory tone of the hippocampus creating an environment conducive to seizure generation and propagation. |
