Neurology 1999;52:453
© 1999 American Academy of Neurology
Articles
Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy
G. W. Mathern, MD,
D. Mendoza, BS,
A. Lozada, BS,
J. K. Pretorius, MS,
Y. Dehnes, MS,
N. C. Danbolt, MD, PhD,
N. Nelson, PhD,
J. P. Leite, MD, PhD,
L. Chimelli, MD,
D. E. Born, MD, PhD,
A. C. Sakamoto, MD,
J. A. Assirati, MD,
I. Fried, MD, PhD,
W. J. Peacock, MD,
G. A. Ojemann, MD and
P. D. Adelson, MD
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.
This article has been cited by other articles:
|
|
|
|
 
W. Zhang, R. Yamawaki, X. Wen, J. Uhl, J. Diaz, D. A. Prince, and P. S. Buckmaster
Surviving Hilar Somatostatin Interneurons Enlarge, Sprout Axons, and Form New Synapses with Granule Cells in a Mouse Model of Temporal Lobe Epilepsy
J. Neurosci.,
November 11, 2009;
29(45):
14247 - 14256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-G. Lee, Z.-Z. Su, L. Emdad, P. Gupta, D. Sarkar, A. Borjabad, D. J. Volsky, and P. B. Fisher
Mechanism of Ceftriaxone Induction of Excitatory Amino Acid Transporter-2 Expression and Glutamate Uptake in Primary Human Astrocytes
J. Biol. Chem.,
May 9, 2008;
283(19):
13116 - 13123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. Oberheim, G.-F. Tian, X. Han, W. Peng, T. Takano, B. Ransom, and M. Nedergaard
Loss of Astrocytic Domain Organization in the Epileptic Brain
J. Neurosci.,
March 26, 2008;
28(13):
3264 - 3276.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mallolas, O. Hurtado, M. Castellanos, M. Blanco, T. Sobrino, J. Serena, J. Vivancos, J. Castillo, I. Lizasoain, M. A. Moro, et al.
A polymorphism in the EAAT2 promoter is associated with higher glutamate concentrations and higher frequency of progressing stroke
J. Exp. Med.,
March 20, 2006;
203(3):
711 - 717.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Ragozzino, E. Palma, S. Di Angelantonio, M. Amici, A. Mascia, A. Arcella, F. Giangaspero, G. Cantore, G. Di Gennaro, M. Manfredi, et al.
Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy
PNAS,
October 18, 2005;
102(42):
15219 - 15223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Williamson, P. R. Patrylo, J. Pan, D. D. Spencer, and H. Hetherington
Correlations between granule cell physiology and bioenergetics in human temporal lobe epilepsy
Brain,
May 1, 2005;
128(5):
1199 - 1208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. S. van der Hel, R. G.E. Notenboom, I. W.M. Bos, P. C. van Rijen, C. W.M. van Veelen, and P. N.E. de Graan
Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy
Neurology,
January 25, 2005;
64(2):
326 - 333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Palma, D. A. Ragozzino, S. Di Angelantonio, G. Spinelli, F. Trettel, A. Martinez-Torres, G. Torchia, A. Arcella, G. Di Gennaro, P. P. Quarato, et al.
Phosphatase inhibitors remove the run-down of {gamma}-aminobutyric acid type A receptors in the human epileptic brain
PNAS,
July 6, 2004;
101(27):
10183 - 10188.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Fujiwara-Tsukamoto, Y. Isomura, K. Kaneda, and M. Takada
Synaptic interactions between pyramidal cells and interneurone subtypes during seizure-like activity in the rat hippocampus
J. Physiol.,
June 15, 2004;
557(3):
961 - 979.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Arellano, A. Munoz, I. Ballesteros-Yanez, R. G. Sola, and J. DeFelipe
Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus
Brain,
January 1, 2004;
127(1):
45 - 64.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Isomura, Y. Fujiwara-Tsukamoto, and M. Takada
Glutamatergic Propagation of GABAergic Seizure-Like Afterdischarge in the Hippocampus In Vitro
J Neurophysiol,
October 1, 2003;
90(4):
2746 - 2751.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Sayin, S. Osting, J. Hagen, P. Rutecki, and T. Sutula
Spontaneous Seizures and Loss of Axo-Axonic and Axo-Somatic Inhibition Induced by Repeated Brief Seizures in Kindled Rats
J. Neurosci.,
April 1, 2003;
23(7):
2759 - 2768.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-z. Su, M. Leszczyniecka, D.-c. Kang, D. Sarkar, W. Chao, D. J. Volsky, and P. B. Fisher
Insights into glutamate transport regulation in human astrocytes: Cloning of the promoter for excitatory amino acid transporter 2 (EAAT2)
PNAS,
February 18, 2003;
100(4):
1955 - 1960.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. A. C. Petroff
Book Review: GABA and Glutamate in the Human Brain
Neuroscientist,
December 1, 2002;
8(6):
562 - 573.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. F. Behrens, P. Franz, B. Woodman, K. S. Lindenberg, and G. B. Landwehrmeyer
Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation
Brain,
August 1, 2002;
125(8):
1908 - 1922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Proper, G. Hoogland, S. M. Kappen, G. H. Jansen, M. G. A. Rensen, L. H. Schrama, C. W. M. van Veelen, P. C. van Rijen, O. van Nieuwenhuizen, W. H. Gispen, et al.
Distribution of glutamate transporters in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy
Brain,
January 1, 2002;
125(1):
32 - 43.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. R. Patrylo, D. D. Spencer, and A. Williamson
GABA Uptake and Heterotransport Are Impaired in the Dentate Gyrus of Epileptic Rats and Humans With Temporal Lobe Sclerosis
J Neurophysiol,
April 1, 2001;
85(4):
1533 - 1542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Loup, H.-G. Wieser, Y. Yonekawa, A. Aguzzi, and J.-M. Fritschy
Selective Alterations in GABAA Receptor Subtypes in Human Temporal Lobe Epilepsy
J. Neurosci.,
July 15, 2000;
20(14):
5401 - 5419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Gross and W. H. Theodore
""The seat of the discharge"" and the molecules that govern seizures
Neurology,
February 1, 1999;
52(3):
441 - 441.
[Full Text]
|
|
|
|
