Alternative splicing of the NMDAR1 glutamate receptor subunit in human temporal lobe epilepsy.
It has been demonstrated in animal models that chronic epilepsy is associated with increased excitability which may result from abnormal glutamatergic transmission involving altered properties of N-methyl-D-aspartate (NMDA) receptors. We have investigated whether human temporal lobe epilepsy is associated with changes in the NMDA receptor at the molecular level by assessing the relative expression of mRNAs of the different splice variants at the N-terminal (exon 5) and C-terminal (exon 21) position for the NMDAR1 subunit. Specimens of hippocampus and temporal lobe cortex from patients with refractory epilepsy were obtained during neurosurgical operations and analyzed by means of the reverse transcription reaction followed by polymerase chain reaction. Non-epileptic control specimens obtained at autopsy exhibited a relatively high level in expression of exon 5-lacking (hippocampus: 0.87; cortex: 0.81) and exon 21-containing (hippocampus: 0.95; cortex: 0.93) transcripts. The ratio for these alternatively spliced transcripts was not significantly changed in epileptic hippocampal and cortical tissues relative to the corresponding non-epileptic samples. These results did not support a potential role for NMDAR1 splice variants in the pathophysiology of epilepsy.
Musshoff
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Institut für Physiologie der Universität Münster, Robert-Koch-Str. 27a, 48149, Münster, Germany. mushoff@uni-muenster.de
Schünke
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Köhling
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Speckmann
E J
EJ
D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D001932:Brain Neoplasms / Q000150:complications / Q000601:surgery; D002648:Child; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D005091:Exons; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013702:Temporal Lobe / Q000378:metabolism*
D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1