Objective: In the present study, therefore, we examined the relationship between CaMKII and NR2B in levodopa-induced dyskinesia rats.

Background: Long-term treatment with L-dopa leads to involuntary aimless movements called L-dopa-induced dyskinesia (LID) has hindered its use in Parkinson’s disease (PD) patients. Emerging evidence suggests a possible role of CaMKIIa and its interacting partners in the development of LID.

Methods: To address this issue, we produced a rat model of PD, and valid PD rats were intrastriatal administrated with different doses of KN-93 (CaMKIIa inhibitor, 5 ug/kg and 10 ug/kg) and MK-801 (NR2B receptor antagonist, 0.1 mg/kg and 0.3 mg/kg), respectively.

Results: We found that CaMKIIa was found to form complexes with NR2B after chronic administration of L-dopa in adult rat striatal neurons. Intrastriatal injection of KN-93 significantly reduced the level of NR2B in CaMKIIa precipitates with a dose dependent response, as well as reduced the Global ALO AIM score without ablation of the therapeutic response to L-dopa. In parallel, intrastriatal injection of MK-801 significantly alleviated the level of CaMKIIa in NR2B precipitates compared to LID group (p < 0.01), and this is accompanied by realizing improvement of the Global ALO AIM score also without affect the efficacy of L-dopa.

Conclusions: In summary, the present study indicated that CaMKIIa-NR2B interaction had an important role in the development of LID. Disrupt of this link by intrastriatal infusion of KN-93 or MK-801 ameliorated dyskinesia in 6-OHDA-lesioned PD rats.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/modulation-of-camkiia-nr2b-interaction-in-levodopa-induced-dyskinesia-in-6-ohda-lesioned-parkinsons-rats/