Assessment of the neurotrophic effects exerted by GDNF following delivery of neurotrophin-secreting stem cells to the rat brain in the lipopolysaccharide model of Parkinson’s disease

Abstract

Event Abstract Back to Event Assessment of the neurotrophic effects exerted by GDNF following delivery of neurotrophin-secreting stem cells to the rat brain in the lipopolysaccharide model of Parkinson’s disease Deirdre B. Hoban1, 2, Linda Howard3 and Eilis Dowd1, 2* 1 National University of Ireland, Galway, Pharmacology & Therapeutics, Ireland 2 NCBES Galway Neuroscience Centre, Ireland 3 National University of Ireland, Galway, Regenerative Medicine Institute (REMEDI), Ireland The delivery method of GDNF has hampered its efficacy as a neuroprotectant in Parkinson’s disease(PD). Ex vivo gene therapy, in which suitable cells, such as bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress GDNF prior to transplantation may be more beneficial for GDNF delivery than direct brain infusion of the neurotrophin. In this study, we used an inflammatory model of PD (the lipopolysaccharide model) to assess the ability of transplanted GDNF-GFP-MSCs to protect against LPS-induced neuroinflammation, neurodegeneration and behavioural impairment. 30 male Sprague Dawley rats were used in this experiment. Motor performance was assessed daily using Stepping and Whisker tests pre- and post-surgery. Rats were performance matched into 3 groups (LPS, LPS + GFP-MSCs, LPS + GDNF-GFP-MSCs; n=10/group). Both cell groups received a transplant of either 200,000 GFP-MSCs or 200,000 GDNF-GFP-MSCs. One day post-transplantation, all rats received a unilateral infusion of LPS (10µg in 2µl sterile saline) into the substantia nigra. Rats were sacrificed by transcardial perfusion-fixation and their brains processed for post-mortem quantitative immunohistochemistry. Injection of LPS into the substantia nigra induced a pronounced inflammatory response which resulted in 20% loss of nigrostriatal dopaminergic neurons and a mild, transient effect on contralateral motor dysfunction. While neither GFP-MSCs nor GDNF-GFP-MSCs transplanted into the striatum protected against motor dysfunction or the nigrostriatal pathway as a whole, dense areas of TH-staining proximal to the transplant site were observed. Importantly, this effect was observed only in the GDNF-GFP-MSC transplanted group. This demonstrates protection and/or sprouting of the dopaminergic terminals induced by trophic effects of secreted GDNF in the LPS-lesioned rats and thus highlights the potential of ex vivo gene therapy using GDNF-GFP-MSCs. Acknowledgements This research was funded by Science Foundation Ireland (11/RFP/NES/3183). Keywords: Lipopolysaccharides, Neuroinflammation, neurodegeneration, Parkinson's disease, Glial Cell Line-Derived Neurotrophic Factor, Neuroprotection Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014. Presentation Type: Poster Presentation Topic: Early Career Neuroscience Citation: Hoban DB, Howard L and Dowd E (2014). Assessment of the neurotrophic effects exerted by GDNF following delivery of neurotrophin-secreting stem cells to the rat brain in the lipopolysaccharide model of Parkinson’s disease. Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00019 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: 12 Sep 2014; Published Online: 12 Sep 2014. * Correspondence: Dr. Eilis Dowd, National University of Ireland, Galway, Pharmacology & Therapeutics, Galway, Ireland, eilis.dowd@nuigalway.ie 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 Deirdre B Hoban Linda Howard Eilis Dowd Google Deirdre B Hoban Linda Howard Eilis Dowd Google Scholar Deirdre B Hoban Linda Howard Eilis Dowd PubMed Deirdre B Hoban Linda Howard Eilis Dowd 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.