Levodopa/Benserazide Loaded Microspheres Alleviate L-dopa Induced Dyskinesia through Preventing the Over-Expression of D1R/Shp-2/ERK1/2 Signaling Pathway in a Rat Model of Parkinson's Disease

Frontiers in Aging Neuroscience
Ying WanJing Gan

Abstract

Background: The long-term intermittent Levodopa (L-dopa) stimulation contributes to an aberrant activation of D1 receptor (D1R) mediated extracellular signal-regulated kinases1/2 (ERK1/2) in the striatal medium spiny neurons, resulting in the occurrence of L-dopa induced dyskinesia (LID). Recently, a novel signaling pathway, D1R/Shp-2/ERK1/2, was proposed to be required for the occurrence of LID. Here we designed the study in which two different methods of L-dopa delivery [continuous dopamine stimulation (CDS) vs. intermittent dopamine stimulation] were used to further identify: (1) the role of D1R/Shp-2/ERK1/2 signaling pathway in the occurrence of LID; (2) whether CDS alleviated LID though preventing the over-expression of the D1R/Shp-2/ERK1/2 signaling pathway. Methods: 6-OHDA-lesioned rat models of Parkinson's disease (PD) were randomly divided into two groups to receive intermittent L-dopa stimulation (L-dopa/benserazide standard group, LS group) or CDS (L-dopa/benserazide loaded microspheres, LBM group) for 21 days. Dyskinesia and anti-parkinsonian effect were compared between the two groups through the AIMs assessment and cylinder test. The critical protein changes in the D1R/Shp-2/ERK1/2 signaling pathway were compared ...Continue Reading

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BETA
Protein Extraction

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Quantity One

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