Objective: In this study, we verified whether the interaction of mGluR5 and NR2B exerts an important effect on the development of LID.

Background: L-dopa is the most effective drug for relieving the motor symptoms of Parkinson’s disease (PD). However, the appearance of L-dopa-induced dyskinesia (LID) compromised the use of the drug. Evidence has shown that dysfunction of the glutamatergic system plays a key role in the development of LID and that the use of metabotropic glutamate receptor 5 (mGluR5) antagonists can significantly improve dyskinesia. However, the mechanisms underlying this alleviation are not well understood. In addition, the interaction of glutamate receptors in the striatum appears to be critical for the development of LID.

Methods: We analyzed data from 120 6-OHDA-lesioned SD rats. As the scores assigned for AIMs and parkinsonian disability are non-parametric, the data was analyzed using a Kruskal-Wallis test followed by Dunn’s test for multiple comparisons when comparing data over multiple days or with Mann–Whitney U test. The western blot and Q-PCR data were normally distributed and were analyzed using one-way ANOVA followed by LSD post hoc comparisons when appropriate, as indicated in the figure legends.

Results: In the present study, we found that interaction between mGluR5 and the N-methyl-D-aspartate (NMDA) receptor subunit NR2B was increased in 6-hydroxydopamine-lesioned parkinsonian rats. Disrupting the mGluR5-NR2B interaction via antagonist or Tat peptide administration led to a decrease in synaptic mGluR5-NR2B trafficking. This decreased mGluR5-NR2B interaction was accompanied by a significant reduction in the severity of LID. In addition to the reduced interaction, ERK1/2 phosphorylation levels, PKC protein expression levels, and L-dopa-induced c-fos and prodynorphin (pdyn) mRNA levels in the lesioned striatum were reduced; these molecules have been associated with LID. Significant correlations were observed between abnormal involuntary movement (AIM) scores and the levels of the NR2B-mGluR5 interaction, PKC protein expression and ERK1/2 phosphorylation.

Conclusions: This study supports the hypothesis that the interaction of mGluR5 and NR2B plays an important role in the development of LID, inhibition of the mGluR5-NR2B interaction may contribute to the MTEP- and MK801-induced down-regulation of ALO AIM scores and aid in recovery from LID.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/interaction-between-mglur5-and-nr2b-is-increased-in-6-ohda-parkinsonian-rats-with-l-dopa-induced-dyskinesiainteraction-between-mglur5-and-nr2b-is-increased-in-6-ohda-parkinsonian-rats-with-l-dopa-indu/