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In the present study, a twenty-mer antisense oligonucleotide specific for N-methyl-D-aspartate receptor one (ANR1) was applied to striatal neurons in primary cell culture. The ANR1 was found to be specific and nontoxic. Significant reductions in expression of NR1 mRNA and proteins were resulted after a single dose of ANR1 transcripts. Interestingly, there were reductions in total NR1 proteins but two phosphorylated forms of NR1 proteins at serine 896 and 897 residues were not reduced. There was also no change in the pattern of distribution of NR1 immunoreactivity in the striatal neurons. In addition, significant reductions of NMDA-mediated peak inward current were found after application of a higher concentration of ANR1 (20–100 µM) by patch clamp recordings. The present results indicate that ANR1 is a useful agent in reducing NMDA receptor functions. The present data thus provide detailed cellular and molecular mechanisms to explain our previous findings of amelioration of motor symptoms in a rat model of Parkinson’s disease. More importantly, application of ANR1 was also found to display neuroprotective effects of striatal neurons against NMDA-induced excitotoxic cell death. The findings have implications in development of new approach in prevention of cell death in neurodegenerative diseases and new treatments for these diseases.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propio- nate (AMPA)-type glutamate receptors (GluR1–4) are one of the most important ionotropic glutamate receptors in the striatum, a key region of the basal ganglia. The present study investigated the trend of developmental expression of AMPA receptor subunits in the striatum of rats in different developmental stages, i.e., at postnatal day 7 (PND7), PND21 and adult. Perfuse-fixed striatal sections were used. The expression of AMPA subunits was studied by immunofluorescence and reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR revealed that the levels of expression of the GluR1 and GluR3 mRNAs were the same among the age groups. The level of GluR2 mRNA was highest in PND21 rats and lowest in adult. The highest level of GluR4 mRNA was detected in rats at PND7. Similar trends of GluR1, GluR2 and GluR2/3 immunoreactivity expression were observed using commercially available specific antibodies. In addition, a large proportion of parvalbumin-immunoreactive GABAergic interneurons in the striatum were found to display GluR1 immunoreactivity in PND21 and adult rats. In contrast, most of the choline acetyltransferase-immunoreactive cholinergic interneurons were found to display GluR2 immunoreactivity but less GluR1 and no GluR2/3 immunoreactivity in PND21 and adult rats. The present study suggests that there is a distinct pattern of expression of AMPA-type receptor mRNAs and proteins in the rat striatum at different stages of development.

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