Changes in expression of N-methyl-D-aspartate receptor subunits in the ratneostriatum after a single dose of antisense oligonucleotide specific for N-methyl-D-aspartate receptor 1 subunit

In order to investigate the process of gene expression of N-methyl-D-aspart ate glutamate receptor (NMDAR) subunits in the rat neostriatum and how this relates to motor behaviors, a single dose of antisense phosphodiester olig odeoxynucleotide specific for NMDAR 1 was unilaterally applied in the neost riatum in a stereotaxic apparatus. After one day of antisense treatment, ip silateral rotation behaviors that were induced by apomorphine were found in the treated animals. Reductions in the levels of expression of NMDAR1 and NMDAR2A messenger RNAs (NMDAR1: 20.6%; NMDAR2A: 19.7%) were found in the an tisense-treated striatal tissues by reverse transcriptase-polymerase chain reaction. There was no change in the levels of NMDAR2B, NMDAR2C and NMDAR2D messenger RNAs. After two days, western blotting experiments showed that t here were decreases in the levels of expression of NMDAR1 (decreased 27.6%) and NMDAR2A (decreased 19.2%) proteins in the NMDAR1 antisense-treated str iatal tissues. In addition, NMDAR1 immunoreactivity was found to decrease i n intensity in the NMDAR1 antisense-treated neostriatum. At the cellular le vel, the intensity of NMDAR1 immunoreactivity in perikarya of presumed medi um spiny neurons was found to decrease. These results indicate that a single dose of NMDAR1 antisense modifies the expression of NMDAR1 messenger RNA and protein in neurons in the neostriatu m. The modification in the expression of NMDAR 1 has differential effects i n the expression of NMDAR2 subunits. Gene expression of the native NMDAR su bunits is likely to be a dynamic process. The change in gene expression of the NMDAR subunits in the neostriatum may have a profound effect on the mot or behaviors of rats. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.