Abstract
In the clinical treatment of Parkinson’s disease (PD), the emergence of l-DOPA-induced dyskinesia (LID) and other motor symptoms remains a restrictive factor for the use of levodopa (l-DOPA). Our objective was to test the effect of continuous dopaminergic stimulation (CDS) on LID and the mechanism of its effect on the calcium (Ca2+) signaling pathway. 6-OHDA (6-hydroxydopamine)-treated rats were administered 1% CMC-Na, l-DOPA, rotigotine behenate (RGTB), and l-DOPA + RGTB, respectively, for 28 days. During the treatment, the abnormal involuntary movement (AIM) scores were conducted on days 1, 5, 10, 14, 19, 23 and 28 after the first dose. Subsequently, the number of tyrosine hydroxylase (TH)-positive neurons was detected by immunohistochemistry. Additionally, the changes in Ca2+ were detected using a laser confocal technique, and the related proteins, such as neuronal NOS (nNOS), BAX, BCl2, CaMKII, P-CaMKII, and PSD-95, were measured by Western blot. Transmission electron microscopy (TEM) was used to investigate the changes in synaptic structure. The data showed that CDS reduced the AIM scores, increased the expression of TH in the substantia nigra (SN), decreased the expression of nNOS and BAX/BCL2ratio in the striatum, reduced the Ca2+ influx induced by l-DOPA and inhibited the Ca2+ signaling pathways of dopamine neurons in the striatum. Moreover, the overactivity of synapses induced by L-DOPA was inhibited by CDS. These data further support the hypothesis that continuous delivery of a dopamine agonist reduces the risk of LID induction. Moreover, RGTB could be a promising treatment for PD by simulating CDS.
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This project was supported by Yantai University and we thank all authors’ contribution to this manuscript.
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This project was supported by Yantai University. The author(s) disclose receipt of the following financial support for the research, authorship, and/or publication of this article: this work was supported by the “Taishan Industry Leading Talent Laureate”.
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JF and XZ performed the research, analyzed the data, and wrote the manuscript. FT contributed to animal experiments. XY designed and funded the research, and finally approved the submission of this manuscript.
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This study was obtained from the Care and Use of Experimental Animal Research Committee at Yantai University (approval number: YT-YX-2019–0097).
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Fu, J., Zhao, X., Tian, F. et al. Continuous dopaminergic stimulation counteracts l-DOPA-induced overactivity of Ca2+ in 6-OHDA-lesioned rats. Exp Brain Res 240, 1933–1941 (2022). https://doi.org/10.1007/s00221-022-06390-y
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DOI: https://doi.org/10.1007/s00221-022-06390-y