GABAergic neurons and GABA(A)-receptors in temporal lobe epilepsy

Neurochem Int. 1999 May;34(5):435-45. doi: 10.1016/s0197-0186(99)00040-6.


Mesial temporal lobe epilepsy (MTLE) is the most prevalent form of epilepsy, characterized by recurrent complex partial seizures and hippocampal sclerosis. The pathophysiology underlying this disorder remains unidentified. While a loss of benzodiazepine binding sites is a key diagnostic feature of MTLE, experimental studies have shown enhanced inhibitory transmission and increased expression of GABA(A)-receptors, suggesting that compensatory mechanisms are operative in epileptic hippocampus. In the present study, changes in the expression and cellular distribution of major GABA(A)-receptor subunits were investigated in the hippocampus of pilocarpine-treated rats during the phase of spontaneous recurrent seizures. A uniform decrease in GABA(A)-receptor subunit-immunoreactivity was observed in regions of extensive neuronal death (i.e. CA1, CA3, hilus). whereas a prominent increase occurred in the dentate gyrus (DG). Most strikingly, the increase was largest for the alpha3- and alpha5-subunits, which are expressed at very low levels in the DG of control rats, suggesting the formation of novel GABA(A)-receptor subtypes in epileptic tissue. Furthermore, an extensive loss of interneurons expressing the alpha1-subunit, representing presumptive basket cells, was seen in the DG. These changes were very similar to those reported in a novel mouse model of MTLE, based on the unilateral injection of kainic acid into the dorsal hippocampus (Bouilleret et al., 1999). This indicates that the regulation of GABA(A)-receptor expression is related to chronic recurrent seizures, and is not due to the extrahippocampal neuronal damage affecting pilocarpine-treated rats. These results allow causal relationships in the induction and maintenance of chronic recurrent seizures to be distinguished. The loss of a critical number of interneurons in the DG is a possible cause of seizure initiation, whereas the long-lasting upregulation of GABA(A)-receptors in granule cells represents a compensatory response to seizure activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dentate Gyrus / chemistry
  • Dentate Gyrus / metabolism
  • Dentate Gyrus / pathology
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / metabolism*
  • Epilepsy, Temporal Lobe / pathology
  • Hippocampus / chemistry
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Immunoenzyme Techniques
  • Interneurons / pathology
  • Male
  • Neurons / metabolism*
  • Neurons / pathology
  • Pilocarpine
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / analysis
  • Receptors, GABA-A / metabolism*
  • gamma-Aminobutyric Acid / physiology*


  • Receptors, GABA-A
  • Pilocarpine
  • gamma-Aminobutyric Acid