The role of neuroinflammation in α-synuclein-linked dopaminergic neurodegeneration in rat brain

Abstract

Event Abstract Back to Event The role of neuroinflammation in α-synuclein-linked dopaminergic neurodegeneration in rat brain Anke Van Der Perren1*, Francesca Macchi1, James Dooley2, Adrian Liston2, Chris Van Den Haute1 and Veerle Baekelandt1 1 KU Leuven, Neurosciences, Belgium 2 KU Leuven, Department of Microbiology and Immunology, Belgium Alpha-synuclein (α-SYN) is considered a key player in Parkinson’s disease (PD), but the exact relationship between α-SYN aggregation and dopaminergic (DA) neurodegeneration remains unresolved. There is increasing evidence that neuroinflammatory processes are closely linked to DA cell death, but whether the inflammatory process is causally involved in PD or rather reflects secondary consequences of nigrostriatal pathway injury is still under debate. We have recently shown that treatment of rats overexpressing α-SYN in the substantia nigra by means of adeno-associated viral vectors serotype 2/7 (rAAV2/7 A53T α-SYN) with the immunosuppressant FK506 for four weeks significantly increased the survival of dopaminergic neurons (DNs) in the substantia nigra (SN) in a dose-dependent way. In order to further understand this process, we investigated in detail the inflammatory component versus α-SYN aggregation and neurodegeneration by histopathological and FACS analysis, motor behavior and non-invasive PET imaging. No reduction in α-synuclein aggregation was apparent in this time window but FK506 significantly lowered the infiltration of CD4+ and CD8+ T-cells and the number of microglia/ macrophages, suggesting an early role for α-SYN and neuroinflammation in PD pathogenesis. Next, to determine whether T-cell infiltration is causally involved in or simply a consequence of the observed DN degeneration, we are currently comparing the effect of α-SYN overexpression in the SN of rats lacking mature T-cells (FoxN1nu/nu) and their wild type littermates (FoxN1nu/+). In conclusion, a better understanding of the exact role of neuroinflammation in α-SYN-linked DA neurodegeneration will contribute to the development of novel therapeutic strategies for PD. Acknowledgements Research was funded by the IWT-Vlaanderen (IWT SBO/80020), the FWO Vlaanderen (G.0768.10), the Academische Stichting Leuven, by the EC-FP6 program ‘DiMI’ (LSHB-CT-2005-512146), the FP7 RTD project MEFOPA (HEALTH-2009-241791), the FP7 program ‘INMiND’ (HEALTH-F2-2011-278850), the KU Leuven (IOF-KP/07/001, OT/08/052A, IMIR PF/10/017), and the MJFox Foundation (Target validation 2010). Keywords: Neuroinflammation, animal model, T-cells, Parkinson's disease, alpha-Synuclein Conference: 11th National Congress of the Belgian Society for Neuroscience, Mons, Belgium, 22 May - 22 May, 2015. Presentation Type: Oral or Poster presentation Topic: Neuroscience Citation: Van Der Perren A, Macchi F, Dooley J, Liston A, Van Den Haute C and Baekelandt V (2015). The role of neuroinflammation in α-synuclein-linked dopaminergic neurodegeneration in rat brain. Front. Neurosci. Conference Abstract: 11th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2015.89.00042 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Apr 2015; Published Online: 05 May 2015. * Correspondence: PhD. Anke Van Der Perren, KU Leuven, Neurosciences, Leuven, Belgium, anke.vanderperren@med.kuleuven.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anke Van Der Perren Francesca Macchi James Dooley Adrian Liston Chris Van Den Haute Veerle Baekelandt Google Anke Van Der Perren Francesca Macchi James Dooley Adrian Liston Chris Van Den Haute Veerle Baekelandt Google Scholar Anke Van Der Perren Francesca Macchi James Dooley Adrian Liston Chris Van Den Haute Veerle Baekelandt PubMed Anke Van Der Perren Francesca Macchi James Dooley Adrian Liston Chris Van Den Haute Veerle Baekelandt Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.