Selective knockdown of gene expression of N-methyl-D-aspartate receptor one ameliorates parkinsonian motor symptom in 6-hydroxydopamine-lesioned rats

S. K. Lai, T. K.Y. Ng, W. K. Lau, M. S. Yang, Chris K C WONG, Y. S. Chan, Kin Lam YUNG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The present study reported the efficacy of antisense oligonucleotides specific for N-methyl-D-aspartate receptor one (NR1) in reduction of motor symptom in a rat parkinsonian model, the unilateral 6-hydroxydopamine-lesioned rat. Significant reductions in apomorphine-induced contralateral rotation were only seen in the NR1 antisense-treated lesioned rats (after a single intraparenchymal dose of antisense to the lesioned neostriatum; 15nmol in 3μl of saline) at 1 or 2 days after the treatment. No motor effect was seen in the lesioned animals with control treatments (sham, treatment using NR1 sense oligonucleotides, randomized oligonucleotides or saline, respectively). In contrast, significant increases in expression of NR1 mRNA in the lesioned neostriatum were seen in rats with control treatments but not in rats with NR1 antisense treatment. Importantly, in the lesioned neostriatum that was treated with NR1 antisense, a significant reduction in NR1 protein expression was found and NR1 immunoreactivity was seen to reduce in perikarya of presumed striatal medium spiny neurons. The present data indicate that a single dose of NR1 antisense ameliorates motor symptom in the rat model. The efficacy of NR1 antisense is likely to be mediated by a selective knockdown in expression of NR1 mRNA and proteins in the presumed medium spiny neurons.

Original languageEnglish
Pages (from-to)11-22
Number of pages12
JournalNeurochemistry International
Volume45
Issue number1
DOIs
Publication statusPublished - Jul 2004

Scopus Subject Areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

User-Defined Keywords

  • Animal model of Parkinson's disease
  • Drug therapy
  • Gene therapy
  • Glutamate receptor antagonism
  • Neostriatum
  • NMDA receptor

Fingerprint

Dive into the research topics of 'Selective knockdown of gene expression of N-methyl-D-aspartate receptor one ameliorates parkinsonian motor symptom in 6-hydroxydopamine-lesioned rats'. Together they form a unique fingerprint.

Cite this