Objective: To study mechanisms of cellular inflammation and neurodegeneration of EVs derived from patients with PD at different disease stages in cell-based disease models.
Background: There is extensive and growing evidence about the role of inflammation in Parkinson`s disease (PD). In addition to neuroinflammatory processes occurring in the brain, such as microglia activation, elevated levels of pro-inflammatory factors are also present in the plasma of PD patients. Extracellular vesicles (EV), secreted membrane particles involved in cell-to-cell communication, carry important information on immunity and its dysregulations. We, therefore, hypothesized that circulating EVs might play a functional role in causing neurodegeneration through immune/inflammation regulation
Method: EVs were isolated from human plasma using size exclusion chromatography, and NTA was used to determine their concentration and size. We then exposed the neuronal cell line(differentiated SHSY5Y) to DiR labeled-plasmatic PD and HC-derived EVs to allow internalization. Fluorescent intensities were analyzed at a wavelength of 750 nm by cytoflex. We also assess their cell viability and morphological changes using immunofluorescence and flow cytometry.
Results: Nanoparticle tracking analysis showed no significant difference in the concentration and size of HC-derived and PD-derived EVs. Flow cytometry showed that DiR-labeled EVs (PD-EVs and HC-EVs) were efficiently incorporated into SHSY5Y. The internalization was increased time-dependently and was highest at 24h. PD-derived EVs significantly reduce axonal growth in SHSY5Y cells compared to HC-derived EVs. The apoptosis/necrosis was also increased in SHSY5Y cells when exposed to PD-derived EVs compared to HC-derived EVs.
Conclusion: We report that fluorescently labeled EVs from the plasma of PD were more readily internalized by SHSY5Y cells. These plasmatic PD-EVs have a toxic effect on neuronal cell lines in vitro, as measured by axonal growth reduction and reduced cell viability
To cite this abstract in AMA style:
A. Yadav, E. Vacchi, S. Pinton, A. Kaelin-Lang, G. Melli. Study of the functional role of circulating extracellular vesicles as mediators of inflammation in cellular models of Parkinson`s disease [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/study-of-the-functional-role-of-circulating-extracellular-vesicles-as-mediators-of-inflammation-in-cellular-models-of-parkinsons-disease/. Accessed June 14, 2025.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/study-of-the-functional-role-of-circulating-extracellular-vesicles-as-mediators-of-inflammation-in-cellular-models-of-parkinsons-disease/