Neuroprotective Effects of Antisense Oligodeoxynucleotides on the G1uN1 Subunit of the N-Methyl-D-Aspartate Receptor

We investigated the neuroprotective effects of antisense oligodeoxynucleotides (AsODN) (5'-cagcaggtgcatggtgct-3') and sense oligodeoxynucleotides (sODN) (5'-ctacaacgtacaagtagt-3') (10(-8) M) on the NMDA receptor subunit GluN1 in olfactory cortical slices of Wistar rats under 10-min anoxia and in the model of glutamate excitotoxicity (L-glutamate, 20 mM). Alterations of NMDA potential amplitudes after preliminary incubation of slices with AsODN and sODN for 360 min were analyzed. Ten-minute anoxia resulted in almost complete suppression of NMDA potentials. After the preincubation with AsODN and subsequent 10-min anoxia the mean amplitude of NMDA potentials was 46 +/- 6% of the control value. Pretreatment of slices with sODN did not restore the NMDA potentials blocked by anoxia. Application of L-glutamate (20 mM) resulted in a blockade of the NMDA potentials, while in slices pretreated with AsODN L-glutamate (20 mM) suppressed the amplitude only to 67 +/- 7% of the control level. Incubation of slices with sODN before the L-glutamate application restored the NMDA potential amplitudes only to 29 +/- 7% of the control value. The obtained data indicate that AsODN exhibits pronounced neuroprotective properties in the conditions of severe anoxia and in the model of glutamate excitotoxicity.