Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson's disease using electrophysiological measurements of visual processing
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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. / Østergaard, Freja Gam; Himmelberg, Marc M; Laursen, Bettina; Siebner, Hartwig R; Wade, Alex R; Christensen, Kenneth Vielsted.
In: Scientific Reports, Vol. 10, 11869, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson's disease using electrophysiological measurements of visual processing
AU - Østergaard, Freja Gam
AU - Himmelberg, Marc M
AU - Laursen, Bettina
AU - Siebner, Hartwig R
AU - Wade, Alex R
AU - Christensen, Kenneth Vielsted
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Animals
KW - Biomarkers
KW - Dependovirus/genetics
KW - Disease Models, Animal
KW - Electrophysiological Phenomena
KW - Evoked Potentials, Visual
KW - Female
KW - Gene Expression
KW - Genetic Vectors/genetics
KW - Humans
KW - Immunohistochemistry
KW - Machine Learning
KW - Mice, Transgenic
KW - Parkinson Disease/etiology
KW - Rats
KW - Visual Cortex
KW - Visual Perception
KW - alpha-Synuclein/genetics
U2 - 10.1038/s41598-020-68808-3
DO - 10.1038/s41598-020-68808-3
M3 - Journal article
C2 - 32681050
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 11869
ER -
ID: 257039533