Brain, Vol 120, Issue 11 1937-1959, Copyright © 1997 by Oxford University Press
GW Mathern, JK Pretorius, HI Kornblum, D Mendoza, A Lozada, JP Leite, LM Chimelli, I Fried, AC Sakamoto, JA Assirati, MF Levesque, PD Adelson and WJ Peacock
This study was designed to determine whether hippocampal neuronal AMPA
(alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and NMDA (N-
methyl-D-aspartate) mRNA levels were differentially increased in temporal
lobe epilepsy patients compared with those measured in control tissue from
non-seizure autopsies. Hippocampi from hippocampal sclerosis patients (n =
28) and temporal mass lesion cases (n = 12) were compared with those from
the autopsies (n = 4), and studied for AMPA GluR1-3 and NMDAR1-2 mRNAs
using semi-quantitative in situ hybridization, along with fascia dentata
and Ammon's horn neuron densities. Compared with the autopsies, and without
correction for neuron counts, the mass lesion cases with neuron densities
similar to autopsies showed: (i) significantly increased NMDAR2
hybridization densities for fascia dentata granule cells; (ii) increased
AMPA GluR3 mRNA densities for Ammon's horn pyramids; and (iii) similar or
numerically increased mRNAs for all other subunits and hippocampal
subfields. Compared with the autopsies, hippocampal sclerosis cases with
decreased neuron densities showed: (i) significantly decreased AMPA GluR1-2
and NMDAR1-2 hybridization densities for Ammon's horn pyramids and (ii)
similar or numerically decreased mRNAs for all other subunits and
subfields. However, correcting for changes in neuron densities showed that
hippocampal sclerosis patients had increased AMPA and NMDA mRNA levels per
neuron compared with autopsies, and in the CA2 resistant sector GluR2 mRNA
levels were numerically greater than autopsies and mass lesion cases.
Furthermore, relative to autopsies both sclerosis and mass lesion
hippocampi showed that, in the stratum granulosum, the greatest mRNA
increases were in AMPA GluR1 and NMDAR2 compared with the other mRNAs. In
chronic temporal lobe seizure patients these results indicate that mass
lesion and sclerosis cases show differential increases in hippocampal AMPA
and NMDA mRNA levels per neuron compared with autopsies, especially for
AMPA GluR1 and NMDAR2 in fascia dentata granule cells. These findings
support the hypothesis that temporal lobe seizures are associated with
increased ionotropic glutamate receptor mRNA levels and alterations in
receptor subunit composition that probably contribute to neuronal
hyperexcitability, synchronization and seizure generation.
ARTICLES
Human hippocampal AMPA and NMDA mRNA levels in temporal lobe epilepsy patients
Department of Neurology, University of California, USA.
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