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Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson’s disease using electrophysiological measurements of visual processing

Biomarkers suitable for early diagnosis and monitoring disease progression are the cornerstone of developing disease-modifying treatments for neurodegenerative diseases such as Parkinson’s disease (PD). Besides motor complications, PD is also characterized by deficits in visual processing. Here, we...

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Autores principales: Østergaard, Freja Gam, Himmelberg, Marc M., Laursen, Bettina, Siebner, Hartwig R., Wade, Alex R., Christensen, Kenneth Vielsted
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368019/
https://www.ncbi.nlm.nih.gov/pubmed/32681050
http://dx.doi.org/10.1038/s41598-020-68808-3
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author Østergaard, Freja Gam
Himmelberg, Marc M.
Laursen, Bettina
Siebner, Hartwig R.
Wade, Alex R.
Christensen, Kenneth Vielsted
author_facet Østergaard, Freja Gam
Himmelberg, Marc M.
Laursen, Bettina
Siebner, Hartwig R.
Wade, Alex R.
Christensen, Kenneth Vielsted
author_sort Østergaard, Freja Gam
collection PubMed
description Biomarkers suitable for early diagnosis and monitoring disease progression are the cornerstone of developing disease-modifying treatments for neurodegenerative diseases such as Parkinson’s disease (PD). Besides motor complications, PD is also characterized by deficits in visual processing. Here, we investigate how virally-mediated overexpression of α-synuclein in the substantia nigra pars compacta impacts visual processing in a well-established rodent model of PD. After a unilateral injection of vector, human α-synuclein was detected in the striatum and superior colliculus (SC). In parallel, there was a significant delay in the latency of the transient VEPs from the affected side of the SC in late stages of the disease. Inhibition of leucine-rich repeat kinase using PFE360 failed to rescue the VEP delay and instead increased the latency of the VEP waveform. A support vector machine classifier accurately classified rats according to their `disease state’ using frequency-domain data from steady-state visual evoked potentials (SSVEP). Overall, these findings indicate that the latency of the rodent VEP is sensitive to changes mediated by the increased expression of α-synuclein and especially when full overexpression is obtained, whereas the SSVEP facilitated detection of α-synuclein across reflects all stages of PD model progression.
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spelling pubmed-73680192020-07-20 Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson’s disease using electrophysiological measurements of visual processing Østergaard, Freja Gam Himmelberg, Marc M. Laursen, Bettina Siebner, Hartwig R. Wade, Alex R. Christensen, Kenneth Vielsted Sci Rep Article Biomarkers suitable for early diagnosis and monitoring disease progression are the cornerstone of developing disease-modifying treatments for neurodegenerative diseases such as Parkinson’s disease (PD). Besides motor complications, PD is also characterized by deficits in visual processing. Here, we investigate how virally-mediated overexpression of α-synuclein in the substantia nigra pars compacta impacts visual processing in a well-established rodent model of PD. After a unilateral injection of vector, human α-synuclein was detected in the striatum and superior colliculus (SC). In parallel, there was a significant delay in the latency of the transient VEPs from the affected side of the SC in late stages of the disease. Inhibition of leucine-rich repeat kinase using PFE360 failed to rescue the VEP delay and instead increased the latency of the VEP waveform. A support vector machine classifier accurately classified rats according to their `disease state’ using frequency-domain data from steady-state visual evoked potentials (SSVEP). Overall, these findings indicate that the latency of the rodent VEP is sensitive to changes mediated by the increased expression of α-synuclein and especially when full overexpression is obtained, whereas the SSVEP facilitated detection of α-synuclein across reflects all stages of PD model progression. Nature Publishing Group UK 2020-07-17 /pmc/articles/PMC7368019/ /pubmed/32681050 http://dx.doi.org/10.1038/s41598-020-68808-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Østergaard, Freja Gam
Himmelberg, Marc M.
Laursen, Bettina
Siebner, Hartwig R.
Wade, Alex R.
Christensen, Kenneth Vielsted
Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson’s disease using electrophysiological measurements of visual processing
title Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson’s disease using electrophysiological measurements of visual processing
title_full Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson’s disease using electrophysiological measurements of visual processing
title_fullStr Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson’s disease using electrophysiological measurements of visual processing
title_full_unstemmed Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson’s disease using electrophysiological measurements of visual processing
title_short Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson’s disease using electrophysiological measurements of visual processing
title_sort classification of α-synuclein-induced changes in the aav α-synuclein rat model of parkinson’s disease using electrophysiological measurements of visual processing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368019/
https://www.ncbi.nlm.nih.gov/pubmed/32681050
http://dx.doi.org/10.1038/s41598-020-68808-3
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