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 - Ostergaard, Freja Gam

AU - Himmelberg, Marc M.

AU - Laursen, Bettina

AU - Siebner, Hartwig R.

AU - Wade, Alex R.

AU - Christensen, Kenneth Vielsted

PY - 2020/7/17

Y1 - 2020/7/17

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 - SUBSTANTIA-NIGRA

KW - SUPERIOR COLLICULUS

KW - EVOKED-POTENTIALS

KW - GAIN-CONTROL

KW - PROJECTION

KW - PATHOLOGY

KW - DOPAMINE

U2 - 10.1038/s41598-020-68808-3

DO - 10.1038/s41598-020-68808-3

M3 - Article

VL - 10

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 11869

ER -