In vitro α-synuclein neurotoxicity and spreading among neurons and astrocytes using Lewy body extracts from Parkinson disease brains
| Autor: | Benjamin Dehay, Paula Ramos-Gonzalez, Francesca De Giorgi, Carlos Matute, Fabio Cavaliere, Mathieu Bourdenx, Loic Cerf, Jose A. Obeso, Erwan Bezard, Alban Bessede, François Ichas |
|---|---|
| Přispěvatelé: | Departamento de Neurociencias, Achucarro Basque Center for Neuroscience, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC)-Instituto de Salud Carlos III [Madrid] (ISC), ImmuSmol, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), HM Centro Integral de Neurociencias A.C. (CINAC), HM Puerta del Sur and CIBERNED and CEU-San Pablo, San Pablo University Madrid, Motac Neuroscience, Manchester, United Kingdom., Motac Neuroscience, Dehay, Benjamin, Instituto de Salud Carlos III [Madrid] (ISC), Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), ImmuSmol [Pessac] (IS), Motac Neuroscience [Manchester, UK], Universidad del Pais Vasco, Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (Ciberned) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell type [SDV]Life Sciences [q-bio] Endocytic cycle Endogeny High-throughput Disease Biology lcsh:RC321-571 Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Pregnancy medicine Animals Humans 96-well plate lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Cells Cultured Synucleinopathies α-Synuclein Neurons Lewy body Neurotoxicity Brain Parkinson Disease medicine.disease In vitro 3. Good health Rats [SDV] Life Sciences [q-bio] 030104 developmental biology Neurology nervous system Microfluidic High content imaging Astrocytes alpha-Synuclein Female Lewy Bodies Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neurobiology of Disease, Vol 103, Iss, Pp 101-112 (2017) Neurobiology of Disease Neurobiology of Disease, Elsevier, 2017, 103, pp.101-112. ⟨10.1016/j.nbd.2017.04.011⟩ Neurobiology of Disease, 2017, 103, pp.101-112. ⟨10.1016/j.nbd.2017.04.011⟩ |
| ISSN: | 1095-953X 0969-9961 |
| DOI: | 10.1016/j.nbd.2017.04.011⟩ |
| Popis: | International audience; Synucleinopathies are a group of diseases characterized by the presence of intracellular protein aggregates containing α-synuclein (α-syn). While α-syn aggregates have been shown to induce multimodal cellular dysfunctions, uptake and transport mechanisms remain unclear. Using high-content imaging on cortical neurons and astrocytes, we here define the kinetics of neuronal and astrocytic abnormalities induced by human-derived α-syn aggregates grounding the use of such system to identify and test putative therapeutic compounds. We then aimed at characterizing uptake and transport mechanisms using primary cultures of cortical neurons and astrocytes either in single well or in microfluidic chambers allowing connection between cells and cell-types. We report that astrocytes take up α-syn-aggregates far more efficiently than neurons through an endocytic event. We also highlight that active α-syn transport occurs between cells and any cell-types. Of special interest regarding the disease, we also show that uptake and spreading of α-syn from astrocytes to neurons can lead to neuronal death. Altogether, we here show that patients-derived α-synuclein aggregates, which are taken up by neurons and astrocytes, induce a differential endogenous response in the two cell types including a peculiar astrocytic toxic gain-of-function that leads to neuronal death. |
| Databáze: | OpenAIRE |
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