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From the Division of Neurosurgery (Drs. Mathern, Fried, and Peacock) and The Brain Research Institute (D. Mendoza, A. Lozada, and J.K. Pretorius), University of California, Los Angeles, CA; the Departments of Pathology (Dr. Chimelli), Neurology (Drs. Leite and Sakamoto), and Neurosurgery (Dr. Assirati), Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, Brazil; the Department of Neurosurgery (Dr. Adelson), University of Pittsburgh, PA; the Departments of Pathology-Neuropathology (Dr. Born) and Neurosurgery (Dr. Ojemann), University of Washington School of Medicine, Seattle, WA; Anatomical Institute (Y. Dehnes and Dr. Danbolt), University of Oslo, Norway; and the Department of Biochemistry (Dr. Nelson), Tel Aviv University, Israel.
Address correspondence and reprint requests to Dr. Gary W. Mathern, Division of Neurosurgery, Reed Neurological Research Center, UCLA Medical Center, Los Angeles, CA 90095-1769; e-mail: gmathern{at}ucla.edu
OBJECTIVE: Sodium-coupled transporters remove extracellular neurotransmitters and alterations in their function could enhance or suppress synaptic transmission and seizures. This study determined hippocampal gamma-aminobutyric acid (GABA) and glutamate transporter immunoreactivity (IR) in temporal lobe epilepsy (TLE) patients.
METHODS: Hippocampal sclerosis (HS) patients (n = 25) and non-HS cases (mass lesion and cryptogenic; n = 20) were compared with nonseizure autopsies (n = 8). Hippocampal sections were studied for neuron densities along with IR for glutamate decarboxylase (GAD; presynaptic 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 transporters).
RESULTS: Compared with autopsies, non-HS cases with similar neuron counts showed: 1) increased GAD IR gray values (GV) in the fascia dentata outer molecular layer (OML), hilus, and stratum radiatum; 2) increased GAT-1 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 neuron densities demonstrated: 1) increased OML and inner molecular layer GAD puncta; 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) increased 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 compared with autopsies. These data support the hypothesis that excitatory and inhibitory neurotransmission and seizure susceptibility could be altered by neuronal and glial transporters in TLE patients.
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