Title Comparative assessment of the motor dysfunction induced by neurotoxic, inflammatory and environmental Parkinson’s disease-related neurotoxins in rats

Abstract

Event Abstract Back to Event Title Comparative assessment of the motor dysfunction induced by neurotoxic, inflammatory and environmental Parkinson’s disease-related neurotoxins in rats Carol L. Naughton1, 2, 3, Deirdre B. Hoban1, 2, 3, Ruth M. Concannon1, 2, 3, Jennifer Feehan1, Aoife McNulty1, Niamh Moriarty1, Deirdre Rooney1 and Eilís Dowd1, 2, 3* 1 National University of Ireland, Galway, Pharmacology & Therapeutics, Ireland 2 Galway Neuroscience Centre, Ireland 3 National Centre for Biomedical Engineering and Science, NUI Galway, Ireland Background: For almost 50 years, Parkinson’s disease has been modelled in preclinical animals using selective catecholaminergic neurotoxins such as 6-hydroxydopamine and MPTP. However, because these models bear little etiological resemblance to the human condition, more recently, there has been a considerable drive to develop and characterise models with improved validity for the human condition. Two such models are those induced by the bacterial inflammagen, LPS, and the organic pesticide, rotenone. However, these models have been poorly characterised with respect to more established models. Aim: Thus, the aim of this project was to characterise the motor impairments induced by LPS and rotenone with those induced by the classic neurotoxin, 6-hydroxydopamine. Methods: Twenty four male Sprague Dawley rats underwent baseline testing on a variety of tests of lateralised motor function (the Stepping Test, the Whisker Test, the Corridor Test and the Cylinder Test). The rats were then performance-matched into 3 groups for unilateral intrastriatal infusion of 6-hydroxydopamine (28 g, n=8), LPS (20 g, n=8) or rotenone (3.6 g, n=8). Motor testing resumed on the day after lesion surgery and continued for ten weeks. Rats were also tested for amphetamine-induced rotational asymmetry three weeks after lesion surgery. Immunohistochemistry for neurodegeneration, microgliosis and astrocytosis was also performed. Results: Unilateral intra-striatal infusion of all three neurotoxins induced a significant impairment in contralateral motor function which was evident from the first day post lesion. However, the impairment induced by 6-hydroxydopamine was significantly more pronounced and stable than that induced by the other neurotoxins. When the rats were tested for amphetamine-induced rotation (which is the classic test for dopaminergic asymmetry), it was found that the 6-hydroxydopamine and rotenone-lesioned rats rotated significantly in the ipsilateral direction, while LPS-lesioned rats did not rotate at all. There was significant neurodegeneration, microgliosis and astrocytosis in all experimental groups on the side ipsilateral to the lesion. Conclusions: This study demonstrates that there are key differences in the patterns of motor dysfunction induced by different Parkinsonian neurotoxins and their associated neurodegenerative effects. These differences should be taken into consideration when selecting the most appropriate model for Parkinson’s disease preclinical studies. Acknowledgements The authors would like to thank Ms. Kiah McCabe for technical assistance. Keywords: animal models of neurodegenerative disease, lipopolysaccharide, 6-hydroxydopamine, Rotenone, Animal behavioral models Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014. Presentation Type: Oral Presentation Topic: Early Career Neuroscience Citation: Naughton CL, Hoban DB, Concannon RM, Feehan J, McNulty A, Moriarty N, Rooney D and Dowd E (2014). Title Comparative assessment of the motor dysfunction induced by neurotoxic, inflammatory and environmental Parkinson’s disease-related neurotoxins in rats . Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00028 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: 15 Sep 2014; Published Online: 15 Sep 2014. * Correspondence: Dr. Eilís 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 Carol L Naughton Deirdre B Hoban Ruth M Concannon Jennifer Feehan Aoife McNulty Niamh Moriarty Deirdre Rooney Eilís Dowd Google Carol L Naughton Deirdre B Hoban Ruth M Concannon Jennifer Feehan Aoife McNulty Niamh Moriarty Deirdre Rooney Eilís Dowd Google Scholar Carol L Naughton Deirdre B Hoban Ruth M Concannon Jennifer Feehan Aoife McNulty Niamh Moriarty Deirdre Rooney Eilís Dowd PubMed Carol L Naughton Deirdre B Hoban Ruth M Concannon Jennifer Feehan Aoife McNulty Niamh Moriarty Deirdre Rooney Eilís 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.