| First Author | Tokita Y | Year | 1996 |
| Journal | Eur J Neurosci | Volume | 8 |
| Issue | 1 | Pages | 69-78 |
| PubMed ID | 8713451 | Mgi Jnum | J:38582 |
| Mgi Id | MGI:85962 | Doi | 10.1111/j.1460-9568.1996.tb01168.x |
| Citation | Tokita Y, et al. (1996) Characterization of excitatory amino acid neurotoxicity in N-methyl-D-aspartate receptor-deficient mouse cortical neuronal cells. Eur J Neurosci 8(1):69-78 |
| abstractText | Roles and mechanisms of N-methyl-D-aspartate (NMDA) receptors in glutamate neurotoxicity were investigated in cultures of NMDA receptor-deficient cortical neuronal cells. Mutant mice lacking a functional NMDA receptor were generated by gene targeting of the NR1 NMDA receptor subunit. Cortical neuronal cells prepared from wild-type NR1+/+, heterozygous NR1+/- and homozygous mutant NR1-/- mice at 15-17 days of gestation grew indistinguishably from each other. Brief exposures (5 min) of both NR1+/+ and NR1+/- neuronal cells to glutamate or NMDA, but not kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), resulted in widespread neuronal degeneration by the following day. In contrast, neither glutamate nor NMDA treatment caused neuronal degeneration in NR1-/- cells, indicating that NMDA receptors are responsible for rapidly triggered glutamate neurotoxicity. The above four compounds were all effective in inducing the death of NR1+/+ and NR1+/- neuronal cells after prolonged exposure (20-24 h). However, NMDA had no neurotoxic effects on NR1-/- cells, although the other three compounds wer neurotoxic with potencies comparable to those for NR1+/+ and NR1+/- cells. The AMPA and kainate receptors are thus sufficient for inducing slowly triggered glutamate neurotoxicity. Brief exposure of a mixed population of NR1+/+ and NR1-/- neuronal cells to NMDA selectively killed the NMDA receptor-expressing cells without any appreciable effects on neighbouring NMDA receptor-deficient cells. This finding further supports a direct and indispensable role for NMDA receptors in NMDA-evoked neuronal cell death. |
