ONO-2506 Can Delay Levodopa-induced Dyskinesia in the Early Stage.

[Display omitted] • ONO-2506 can delay the emergence of AIMs after L-DOPA administration. • ONO-2506 can reduce the total AIM score and delay LID development. • Interventions targeting astrocytes and glutamate transporters may delay LID. Background : Levodopa-induced dyskinesia (LID) is a common motor complication of levodopa (L-DOPA) treatment for Parkinson's disease (PD). In recent years, the role of astrocytes in LID has increasingly attracted attention. Objective : To explore the effect of an astrocyte regulator (ONO-2506) on LID in a rat model and the potential underlying physiological mechanism. Methods : Unilateral LID rat models, established by administering 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle through stereotactic injection, were injected with ONO-2506 or saline into the striatum through brain catheterization and were administered L-DOPA to induce LID. Through a series of behavioral experiments, LID performance was observed. Relevant indicators were assessed through biochemical experiments. Results : In the LID model of 6-OHDA rats, ONO-2506 significantly delayed the development and reduced the degree of abnormal involuntary movement in the early stage of L-DOPA treatment and increased glial fibrillary acidic protein and glutamate transporter 1 (GLT-1) expression in the striatum compared to saline. However, there was no significant difference in the improvement in motor function between the ONO-2506 and saline groups. Conclusions : ONO-2506 delays the emergence of L-DOPA-induced abnormal involuntary movements in the early stage of L-DOPA administration, without affecting the anti-PD effect of L-DOPA. The delaying effect of ONO-2506 on LID may be linked to the increased expression of GLT-1 in the rat striatum. Interventions targeting astrocytes and glutamate transporters are potential therapeutic strategies to delay the development of LID. [ABSTRACT FROM AUTHOR]

Copyright of Neuroscience is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)