Gene expression of glutamate receptors GluR1 and NR1 is differentially modulated in striatal neurons in rats after 6-hydroxydopamine lesion

S. K. Lai, Y. C. Tse, M. S. Yang, Chris K C WONG, Y. S. Chan, Kin Lam YUNG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

In the present study, we attempted to address the modulation of the gene expression of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors in the neostriatum of the 6-hydroxydopamine (6-OHDA)-lesioned rat, an animal model of Parkinson's disease. After 2 weeks of lesion, reverse transcriptase-polymerase chain reactions (RT-PCRs) revealed significant reduction in GluR1 mRNA expression but a significant enhancement of NR1 mRNA expression in the striatal tissues of the lesioned side. No modulation in the mRNA expression of GluR2, GluR3, GluR4 and NR2B were found. Immunofluorescence with digital imaging analysis also demonstrated a significant reduction in GluR1 immunoreactivity in the lesioned neostriatum. Interestingly, the reduction in GluR1 immunoreactivity was primarily observed in presumed striatal medium spiny neurons but not in parvalbumin-labeled striatal GABAergic interneurons. Immunoreactivity for GluR2, GluR2/3, GluR4, NR1 and NR2B was unchanged in neurons of the neostriatum of the lesioned side. The present results indicate that there is an opposite trend in modulation in the gene expressions of GluR1 and NR1 in the neostriatum of 6-OHDA-lesioned rats after dopamine denervation. Modulation of GluR1 mRNA and immunoreactivity is likely to be limited in the striatal projection neurons. These findings have implications for the use of NMDA and AMPA receptor antagonists in the treatment of Parkinson's disease.

Original languageEnglish
Pages (from-to)639-653
Number of pages15
JournalNeurochemistry International
Volume43
Issue number7
DOIs
Publication statusPublished - Dec 2003

Scopus Subject Areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

User-Defined Keywords

  • Basal ganglia
  • Etiology
  • Ionotropic glutamate receptors
  • Medium spiny neurons
  • Motor symptoms
  • Rat model of Parkinson's disease
  • Striatal interneurons

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