Neuroprotective Effects of Antisense Oligodeoxynucleotides on the GluN1 Subunit of the N-Methyl-D-Aspartate Receptor

We investigated the neuroprotective effects of antisense (AsODN) (5'-CAGCAGGTGCATGGTGCT-3') and sense (sODN) (5'-CTACAACGTACAAGTAGT-3') oligodesoxynucleotides (10(-8) M) on the activity of NMDA receptor subunit GluN1 in Wistar rat olfactory cortical slices exposed to 10-min anoxia and in the model of glutamate excitotoxicity (L-glutamate, 20 mM). The changes of the NMDA potential amplitudes after preincubation the slices with AsODN or sODN for 360 min were analyzed. AsODN and subsequent 10-min anoxia inhibited NMDA potentials by up to 46 +/- 6% as compared to the control. Incubation of slices in the presence of sODN resulted in an irreversible blockade of NMDA potentials. After the application of L-glutamate (20 mM) to the slices treated with AsODN, the NMDA potentials were as high as 67 +/- 7% of the control level, whereas these potentials were blocked in slices treated with L-glutamate only. In slices incubated with sODN L-glutamate suppressed the amplitudes of NMDA potentials to 29 +/- 7% of the control. The data obtained point to neuroprotective properties of AsODN in the conditions of severe anoxia and in the model of glutamate excitotoxicity.