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- Gaceb, Abderahim, et al.
(författare)
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An In Vitro Partial Lesion Model of Differentiated Human Mesencephalic Neurons : Effect of Pericyte Secretome on Phenotypic Markers
- 2020
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Ingår i: Journal of Molecular Neuroscience. - : Springer Science and Business Media LLC. - 0895-8696 .- 1559-1166. ; 70:11, s. 1914-1925
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease (PD) is characterised by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta. Post-mortem data suggests that the loss of DA markers may long precede the cell death, leaving a window to rescue the DA phenotype. Screening for potential neuroprotective or restorative therapies, however, requires that partial lesions of DA neurons can be modelled in vitro. In order to establish a partial lesion model of DA neurons in vitro, we evaluated the effects of different exposure times to 1-methyl-4-phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) on the cell survival and DA marker expression using DA neurons derived from the Lund human mesencephalic (LUHMES) cell line. We show that 24-h incubation with 50 μM of MPP+ or 6-h incubation with 100 μM of 6-OHDA leads to a significant decrease in the protein expression of DA markers without affecting overall cell death, consistent with a mild DA lesion. Using conditioned medium of human brain–derived pericytes stimulated with platelet-derived growth factor BB (PDGF-BB), we demonstrate a significant upregulation of DA markers. In conclusion, we provide an experimental model of an in vitro DA neuron partial lesion suitable to study different molecules and their potential neuroprotective or neurorestorative effects on the DA phenotype. We provide evidence that the secretome of brain pericytes stimulated via PDGF-BB/PDGFRβ affects DA marker expression and may represent one possible mechanism contributing to the neurorestoration previously observed in PD by this growth factor.
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| 2. |
- Ousmaal, Mohamed E.F., et al.
(författare)
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Circulating microparticles released during dyslipidemia may exert deleterious effects on blood vessels and endothelial function
- 2020
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1056-8727. ; 34:10
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To compare the bioactivity of circulating microparticles (MPs) isolated from dyslipidemic Psammomys obesus (P. obesus) fed a high-energy diet (HED) with those released from healthy P. obesus fed a normal diet (ND). Methods: Vascular reactivity of aortic rings was evaluated by myography, after 24 h incubation in the absence or in the presence of circulating MPs isolated, by differential centrifugations, from the plasma of animals subjected to HED (MPsHED) or ND (MPsND) for 12 weeks. Human umbilical vein endothelial cells (HUVECs) were treated for 24 h with MPsHED or MPsND animals and subjected to immunofluorescence staining of caveolin-1 (cav-1), intercellular adhesion molecule-1 (ICAM-1), endothelial nitric oxide synthase (eNOS), F-actin and reactive oxygen species (ROS) detection. Results: The HED exerted a distinctly pronounced hyperlipidemic effect marked by plasmatic increase of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and triglyceride (TG). Both MPsND and MPsHED induced a significant reduction of maximal relaxation induced by acetylcholine (ACh). Interestingly, MPsHED significantly decreased eNOS expression up to ~25% and increased ROS production up to ~75% on in vitro treated HUVECs. Moreover, in HUVECs, MPsHED significantly decreased cav-1 expression up to ~50% whereas significant increase of ICAM-1 expression by about 2-fold approximately was observed. Conclusion: Our experimental study demonstrated the dual role of MPs on vascular function by modulating endothelial cell function. Furthermore, MPs may be considered as vectors of a bioactive information contributing to inflammation and vascular damage.
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