Unchanged glutamine synthetase activity and increased NMDA receptor density in epileptic human neocortex: implications for the pathophysiology of epilepsy.
We investigated whether alterations in glutamate metabolising glutamine synthetase activity occur in human epileptic neocortex, as shown previously for human epileptic hippocampus [Eid, T., Thomas, M.J., Spencer, D.D., Rundén-Pran, E., Lai, J.C.K., Malthankar, G.V., Kim, J.H., Danbolt, N.C., Ottersen, O.P., de Lanerolle, N.C., 2004. Loss of glutamine synthetase in the human epileptic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet 363, 28-37]. Glutamine synthetase activity was equivalent in both non-epileptic and epileptic human neocortex. Epileptic tissue, however, was characterised by a 37% increase in the density of synaptosomal NMDA receptor sites compared to non-epileptic tissue, as revealed by a radioligand binding assay (B max(non-epileptic) 1.45 pmol/mg protein and B max(epileptic) 1.99 pmol/mg protein, P < 0.05). Our findings shed some doubts on a role of glutamine synthetase in the pathophysiology of epilepsy in the neocortex. However, the detection of a significantly reduced enzymatic activity in the epileptic amygdala supports the assumption that the enzyme defect is localized to the epileptic mesial temporal lobe of corresponding patients.
Steffens
Marc
M
Sektion Klinische Neuropharmakologie, Neurozentrum, Breisacherstrasse 64, D-79106 Freiburg, Germany.
Huppertz
Hans-Jürgen
HJ
Zentner
Josef
J
Chauzit
Emmanuelle
E
Feuerstein
Thomas J
TJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000679:Amygdala / Q000378:metabolism* / Q000503:physiopathology; D001667:Binding, Competitive; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism* / Q000503:physiopathology; D011869:Radioligand Assay; D011940:Receptor Aggregation / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase