Decreased expression and functionality of NMDA receptor complexes persist in the CA1, but not in the dentate gyrus after transient cerebral ischemia.
The authors investigated the gene expression of the NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor and the functional electrophysiologic activity of NMDA receptor complexes in the vulnerable CA1 and less vulnerable dentate gyrus subfields of the rat hippocampus at different times after transient cerebral ischemia. Decreased expression for both subtypes was observed in both the CA1 subfield and dentate granule cell layer at early times after challenge; however, the decreased expression in the dentate granule cell layer was reversible because mRNA levels for both the NR2A and NR2B subtypes recovered to, or surpassed, sham-operated mRNA levels by 3 days postchallenge. No recovery of expression for either subtype was observed in the CA1 subfield. The functional activity of NMDA receptor complexes, as assessed by slow field excitatory postsynaptic potentiations (slow f-EPSP) in CA1 pyramidal neurons, was maintained at 6 hours postchallenge; however, this activity was diminished greatly by 24 hours postchallenge, and absent at 7 days postchallenge. A similar pattern was observed for the non-NMDA receptor-mediated fast f-EPSP. In dentate granule neurons, however, no significant change in NMDA receptor-mediated slow f-EPSP from sham control was observed at any time after insult. The non-NMDA receptor-generated fast f-EPSPs also were maintained at all times postinsult in the dentate gyrus. These results illustrate that the activity of NMDA receptors remains functional in dentate granule neurons, but not in the pyramidal neurons of the CA1 subfield, at early and intermediate times after transient cerebral ischemia, and suggest that there is a differential effect of ischemia on the glutamatergic transmission systems in these two hippocampal subfields.
Hsu
J C
JC
Playfair Neuroscience Unit, and Department of Anesthesia, University of Toronto, Ontario, Canada.
Zhang
Y
Y
Takagi
N
N
Gurd
J W
JW
Wallace
M C
MC
Zhang
L
L
Eubanks
J H
JH
D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D016133:Polymerase Chain Reaction; D017966:Pyramidal Cells / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000502:physiology; D013569:Synapses / Q000502:physiology; D014158:Transcription, Genetic
D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate