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http://hdl.handle.net/1942/30373
Title: | Chronic nigral neuromodulation aggravates behavioral deficits and synaptic changes in an α-synuclein based rat model for Parkinson’s disease | Authors: | Torre-Muruzabal, Teresa DEVOGHT, Jens Van Den Haute, Chris Van Der Perren, Anke BRONE, Bert Baekelandt, Veerle |
Issue Date: | 2019 | Publisher: | BMC | Source: | Acta Neuropathologica Communications, 7 (1) (Art N° ARTN 160) | Abstract: | Aggregation of alpha-synuclein (α-SYN) is the pathological hallmark of several diseases named synucleinopathies, including Parkinson's disease (PD), which is the most common neurodegenerative motor disorder. Alpha-SYN has been linked to synaptic function both in physiological and pathological conditions. However, the exact link between neuronal activity, α-SYN toxicity and disease progression in PD is not clear. In this study, we aimed to investigate the effect of chronic neuromodulation in an α-SYN-based rat model for PD using chemogenetics. To do this, we expressed excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) combined with mutant A53T α-SYN, using two different recombinant adeno-associated viral (rAAV) vectors (serotypes 2/7 and 2/8) in rat substantia nigra (SN) and investigated the effect on motor behavior, synapses and neuropathology. We found that chronic neuromodulation aggravates motor deficits induced by α-SYN, without altering dopaminergic neurodegeneration. In addition, neuronal activation led to changes in post-translational modification and subcellular localization of α-SYN, linking neuronal activity to the pathophysiological role of α-SYN in PD. | Keywords: | α-Synuclein;DREADDs;Neuronal activity;Parkinson's disease | Document URI: | http://hdl.handle.net/1942/30373 | ISSN: | 2051-5960 | e-ISSN: | 2051-5960 | DOI: | 10.1186/s40478-019-0814-3 | ISI #: | WOS:000491886700002 | Rights: | © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
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Torre-Muruzabal-2019.pdf | Published version | 2.02 MB | Adobe PDF | View/Open |
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