Title: NEURONAL ACTIVITY MODULATION IN AN ALPHA-SYNUCLEIN-BASED RAT MODEL FOR PARKINSON’S DISEASE.
Abstract: Event Abstract Back to Event NEURONAL ACTIVITY MODULATION IN AN ALPHA-SYNUCLEIN-BASED RAT MODEL FOR PARKINSON’S DISEASE. Teresa Torre1, 2*, Jens Devoght3, 4, Chris Van Den Haute1, 2, Bert Brône3, 4, Anke Van Der Perren1, 2 and Veerle Baekelandt1, 2* 1 KU Leuven, Belgium 2 Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Belgium 3 Biomedical Research Institute, Faculty of Medicine and Life Sciences, University of Hasselt, Belgium 4 BIOMED, Belgium Objectives. The general aim of this study was to investigate the effect of neuromodulation on Parkinson’s disease (PD) pathogenesis. More specifically, we aimed to investigate the relationship between neuronal activity, motor behaviour, alpha-synuclein (αSYN) aggregation and dopaminergic neurodegeneration in a viral vector-based αSYN rat model. Methods. To modulate the neuronal activity we used a chemogenetic tool, namely Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Both αSYN and the DREADDS were overexpressed in the substantia nigra (SN) of the rat using rAAV vectors. We validated the changes in neuronal activity in response to intraperitoneal injection of the agonist clozapine-N-oxide (CNO) using c-fos immunostaining and electrophysiological recordings. CNO was administered for … weeks (indicate time period). Motor performance was assessed using the cylinder test at 1, 2 and 4 weeks after injection. Dopaminergic neurodegeneration and αSYN aggregation were evaluated by immunohistological stainings and biochemical characterization. Results. We found that chronic activation of dopaminergic neurons worsens the motor behaviour in our rAAV-based αSYN rat model. Nevertheless, no significant differences in neuronal cell loss were observed between the chronically stimulated animals and the controls. We are currently investigating differences in αSYN aggregation and phosphorylation. Conclusions. Neuronal modulation appears to aggravate the motor behavioural deficits caused by αSYN overexpression in a viral vector-based rat model. In depth characterization using immunohistochemical and biochemical analysis is currently ongoing to understand the molecular cause of these behavioural changes. Objectives. The general aim of this study was to investigate the effect of neuromodulation on Parkinson’s disease (PD) pathogenesis. More specifically, we aimed to investigate the relationship between neuronal activity, motor behaviour, alpha-synuclein (αSYN) aggregation and dopaminergic neurodegeneration in a viral vector-based αSYN rat model. Methods. To modulate the neuronal activity we used a chemogenetic tool, namely Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Both αSYN and the DREADDS were overexpressed in the substantia nigra (SN) of the rat using rAAV vectors. We validated the changes in neuronal activity in response to intraperitoneal injection of the agonist clozapine-N-oxide (CNO) using c-fos immunostaining and electrophysiological recordings. CNO was administered for 3 weeks. Motor performance was assessed using the cylinder test at 1, 2 and 4 weeks after injection. Dopaminergic neurodegeneration and αSYN aggregation were evaluated by immunohistological stainings and biochemical characterization. Results. We found that chronic activation of dopaminergic neurons worsens the motor behaviour in our rAAV-based αSYN rat model. Nevertheless, no significant differences in neuronal cell loss were observed between the chronically stimulated animals and the controls. We are currently investigating differences in αSYN aggregation and phosphorylation. Conclusions. Neuronal modulation appears to aggravate the motor behavioural deficits caused by αSYN overexpression in a viral vector-based rat model. In depth characterization using immunohistochemical and biochemical analysis is currently ongoing to understand the molecular cause of these behavioural changes. Keywords: synuclein alpha (SNCA), Neuromodulation, DREADDs, synaptic activity, Parkinson ' s disease Conference: 13th National Congress of the Belgian Society for Neuroscience , Brussels, Belgium, 24 May - 24 May, 2019. Presentation Type: Poster presentation Topic: Behavioral/Systems Neuroscience Citation: Torre T, Devoght J, Van Den Haute C, Brône B, Van Der Perren A and Baekelandt V (2019). NEURONAL ACTIVITY MODULATION IN AN ALPHA-SYNUCLEIN-BASED RAT MODEL FOR PARKINSON’S DISEASE.. Front. Neurosci. Conference Abstract: 13th National Congress of the Belgian Society for Neuroscience . doi: 10.3389/conf.fnins.2019.96.00006 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: 01 May 2019; Published Online: 27 Sep 2019. * Correspondence: Miss. Teresa Torre, KU Leuven, Leuven, Belgium, [email protected] Prof. Veerle Baekelandt, KU Leuven, Leuven, Belgium, [email protected] 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 Teresa Torre Jens Devoght Chris Van Den Haute Bert Brône Anke Van Der Perren Veerle Baekelandt Google Teresa Torre Jens Devoght Chris Van Den Haute Bert Brône Anke Van Der Perren Veerle Baekelandt Google Scholar Teresa Torre Jens Devoght Chris Van Den Haute Bert Brône Anke Van Der Perren Veerle Baekelandt PubMed Teresa Torre Jens Devoght Chris Van Den Haute Bert Brône Anke Van Der Perren 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.