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To study the feasibility of plasma extracellular vesicles (EVs) miRNAs as diagnostic biomarkers for Parkinson's disease (PD). Plasma EVs were isolated from 30 PD patients and 30 age- and sex-matched healthy controls. Plasma EVs miRNAs were analysed by qRT-PCR. SH-SY5Y cells were induced by different concentrations of 1-Methyl-4-phenil-pyridinium (MPP+) to obtain PD cellular model. The levels of miRNAs and α-synuclein (α-syn) in PD cellular model were analysed by qRT-PCR and Western blot. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic usefulness of the miRNAs in plasma EVs for PD. The gene ontology (GO) and KEGG pathways of the target genes of miRNAs were analysed by softwares. The level of hsa-miR-30c-2-3p in plasma EVs was significantly higher in PD patients than that in controls, and the levels of hsa-miR-15b-5p, hsa-miR-138-5p, hsa-miR-338-3p, hsa-miR-106b-3p and hsa-miR-431-5p in plasma EVs were lower in PD patients than that in controls. When compared with the control group, the area under the curve (AUC) values for hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p, hsa-miR-431-5p, hsa-miR-338-3p and hsa-miR-106b-3p were all greater than 0.6. The target genes of hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p and hsa-miR-338-3p were enriched in dopaminergic synapse and PD pathway. The hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p, hsa-miR-106b-3p, hsa-miR-338-3p and hsa-miR-431-5p may be used as potential biomarkers for the diagnosis of PD, and the combined diagnostic accuracy of hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p and hsa-miR-106b-3p was better. The target genes of hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p and hsa-miR-338-3p may regulate the expression of dopamine by dopaminergic synapse and PD pathway. Isolation and identification of plasma EVs. The miRNAs in plasma EVs may be used as potential biomarkers for the diagnosis of PD. When SH-SY5Y cells were induced by different concentrations of MPP+, the levels of miRNAs and α-syn changed gradually. The target genes of miRNAs were enriched in dopaminergic synapse and PD pathway. The target genes of miRNAs may regulate the expression of dopamine. [ABSTRACT FROM AUTHOR]

Purpose: Parkinson's disease is a progressive disorder. To investigate the biochemical alterations in the striatum of rats with different stages of Parkinson's disease induced by proteasomal inhibition, we quantified neurochemical profiles of the striatum using proton magnetic resonance spectroscopyusing 9.4 T ultra-high field imaging. Methods: In this study, 10 μg/2 μl lactacystin, a selective proteasome inhibitor, was unilaterally injected stereotaxically into the left substantia nigra pars compacta of rats. An equal volume of saline was injected into the same region and side in the control group. Changes in motor behaviour were observed. The morphological changes of tyrosine hydroxylase-positive cells in substantia nigra pars compacta were visualized using immunohistochemistry. Tyrosine hydroxylase-positive nerve fibers were quantified. Alterations of N-acetylaspartate, choline, creatine, taurine in the different stages of Parkinson's disease rats were detected using proton magnetic resonance spectroscopy. Results: Application of in vivo 1H magnetic resonance spectroscopy was repeated in both the six Parkinson's disease rats and the six control rats across three time points during the first, second and fourth weekend after administration. In Parkinson's disease rats, increased N-acetylaspartate and decreased taurine concentrations were observed in the left striatum at the first week after administration. The increased N-acetylaspartate and choline concentrations were observed at the second weekend. At the fourth weekend, increased creatine concentrations in the left side were observed, while other metabolites were not significantly changed. Conclusions: Neurochemical alterations occurred in the striatum during different stages of the Parkinson's disease model in rats. Also, 9.4 T 1H magnetic resonance spectroscopy may be a useful tool for elucidating the progression of Parkinson's disease through the variation of these metabolites. [ABSTRACT FROM AUTHOR]