Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy

Objective: Sodium-coupled transporters remove extracellular neurotransmitte rs and alterations in their function could enhance or suppress synaptic tra nsmission and seizures. This study determined hippocampal gamma-aminobutyri c acid (GABA) and glutamate transporter immunoreactivity (IR) in temporal l obe epilepsy (TLE) patients. Methods: Hippocampal sclerosis (HS) patients ( n = 25) and non-HS cases (mass lesion and cryptogenic; n = 20) were compare d with nonseizure autopsies (n = 8). Hippocampal sections were studied for neuron densities along with IR for glutamate decarboxylase (GAD; presynapti c GABA terminals), GABA transporter-1 (GAT-1; presynaptic GABA transporter) , GAT-3 (astrocytic GABA transporter), excitatory amino acid transporter 3 (EAAT3; postsynaptic glutamate transporter), and EAAT2-1 (glial glutamate t ransporters). Results: Compared with autopsies, non-HS cases with similar n euron counts showed: 1) increased GAD IR gray values (GV) in the fascia den tata outer molecular layer (OML), hilus, and stratum radiatum; 2) increased GAT-I OML GVs; 3) increased astrocytic GAT-3 GVs in the hilus and Ammon's horn; and 4) no IR differences for EAAT3-1. HS patients with decreased neur on densities demonstrated: 1) increased OML and inner molecular layer GAD p uncta; 2) decreased GAT-1 puncta relative to GAD in the stratum granulosum and pyramidale; 3) increased GAT-1 OML GVs; 4) decreased GAT-3 GVs; 5) incr eased EAAT3 IR on remaining granule cells and pyramids; 6) decreased glial EAAT2 GVs in the hilus and CA1 stratum radiatum associated with neuron loss ; and 7) increased glial EAAT1 GVs in CA2/3 stratum radiatum. Conclusions: Hippocampal GABA and glutamate transporter IR differ in TLE patients compar ed with autopsies. These data support the hypothesis that excitatory and in hibitory neurotransmission and seizure susceptibility could be altered by n euronal and glial transporters in TLE patients.