TY - JOUR
T1 - GABAB receptor autoradiography in hippocampal sclerosis associated with human temporal lobe epilepsy
AU - Billinton, A
AU - Baird, VH
AU - Thom, M
AU - Duncan, JS
AU - Upton, N
AU - Bowery, Norman
PY - 2001/1/1
Y1 - 2001/1/1
N2 - 1. Metabotropic gamma-aminobutyric acid receptors (GABA(B)) exist both pre- and postsynaptically throughout the brain, mediating the suppression of neurotransmitter release and late inhibitory postsynaptic potentials. Investigation of GABA(B) receptors in rodent models of temporal lobe epilepsy (TLE) suggests that expression or function of these receptors may be altered in the disorder. 2. The aim of the present study was to investigate the expression of GABA(B) receptors in samples of hippocampus surgically resected from patients with hippocampal sclerosis (HS) related intractable TLE, and compare this expression with samples of neurologically normal post-mortem (PM) control hippocampal tissue. Appropriate measures of neuronal loss associated with HS were investigated for comparison with receptor binding data. 3. Receptor autoradiography with [(3)H]-GABA in the presence of isoguvacine, and quantitative densitometric analysis were used to investigate GABA(B) receptor expression (B(max)) and affinity (K(D)) in 11 HS samples and eight controls. A three-dimensional cell counting technique was used to assess neuronal density in both groups. 4. GABA(B) receptor density was significantly reduced in CA1, CA2, CA3, hilus and dentate gyrus, and increased in the subiculum, of HS cases as compared with PM controls. Neuronal loss was significant in all regions measured. When adjusted for neuronal loss, CA1 GABA(B) receptor expression appeared significantly upregulated (P:
AB - 1. Metabotropic gamma-aminobutyric acid receptors (GABA(B)) exist both pre- and postsynaptically throughout the brain, mediating the suppression of neurotransmitter release and late inhibitory postsynaptic potentials. Investigation of GABA(B) receptors in rodent models of temporal lobe epilepsy (TLE) suggests that expression or function of these receptors may be altered in the disorder. 2. The aim of the present study was to investigate the expression of GABA(B) receptors in samples of hippocampus surgically resected from patients with hippocampal sclerosis (HS) related intractable TLE, and compare this expression with samples of neurologically normal post-mortem (PM) control hippocampal tissue. Appropriate measures of neuronal loss associated with HS were investigated for comparison with receptor binding data. 3. Receptor autoradiography with [(3)H]-GABA in the presence of isoguvacine, and quantitative densitometric analysis were used to investigate GABA(B) receptor expression (B(max)) and affinity (K(D)) in 11 HS samples and eight controls. A three-dimensional cell counting technique was used to assess neuronal density in both groups. 4. GABA(B) receptor density was significantly reduced in CA1, CA2, CA3, hilus and dentate gyrus, and increased in the subiculum, of HS cases as compared with PM controls. Neuronal loss was significant in all regions measured. When adjusted for neuronal loss, CA1 GABA(B) receptor expression appeared significantly upregulated (P:
KW - receptor autoradiography
KW - temporal lobe epilepsy
KW - hippocampal sclerosis
KW - GABA(B)
U2 - 10.1038/sj.bjp.0703854
DO - 10.1038/sj.bjp.0703854
M3 - Article
C2 - 11159697
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
SN - 1476-5381
VL - 132
SP - 475
EP - 480
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
ER -