Monitoring of a progressive functional dopaminergic deficit in the A53T-AAV synuclein rats by combining 6-[ 18 F]fluoro-L-m-tyrosine imaging and motor performances analysis.
[en] With the emergence of disease-modifying therapies for Parkinson’s disease, reliable longitudinal markers are needed to quantify pathology and demonstrate disease progression. We developed the A53T-AAV rat model of synucleinopathy by combining longitudinal measures over 12 weeks. We first characterized the progression of the motor and dopaminergic deficits. Then, we monitored the disease progression using the [ 18 F]FMT Positron Emission Tomography (PET) radiotracer. The nigral injection of A53T-AAV led to an increase in phosphorylated α-synuclein on S129, a progressive accumulation of α-synuclein aggregates, and a decrease of dopaminergic function associated with a deterioration of motor activity. The longitudinal monitoring of A53T-AAV rats with [ 18 F]FMT PET showed a progressive reduction of the Kc outcome parameter in the caudate putamen from the lesioned side. Interestingly, the progressive reduction in the [18F]FMT PET signal correlated with defects in the stepping test.
In conclusion, we established a progressive rat model of α-synuclein pathology which monitors the
deficit longitudinally using both the [18F]FMT PET tracer and behavioral parameters, 2 features that have strong relevance for translational approaches.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Becker, Guillaume ; Université de Liège - ULiège > Département de Psychologie > Département de Psychologie
Michel, Anne
Bahri, Mohamed Ali ; Université de Liège - ULiège > GIGA CRC In vivo Imaging - Aging & Memory
Mairet-Coello, Georges
Lemaire, Christian ; Université de Liège - ULiège > CRC In vivo Imaging-Radiochemistry
Deprez, Tania
Freyssin, Aline
Jacquin, Lucas
Hustadt, Fabian
De Wolf, Catherine
Caruso, Mélina
Frequin, Jean-Marie
Gillent, Eric
Bezard, Erwan
Garraux, Gaëtan ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie du système nerveux
Luxen, André ; Université de Liège - ULiège > Département de chimie (sciences) > Département de chimie (sciences)
Citron, Martin
Downey, Patrick
Plenevaux, Alain ; Université de Liège - ULiège > GIGA CRC In vivo Imaging - Preclinical Imaging
Monitoring of a progressive functional dopaminergic deficit in the A53T-AAV synuclein rats by combining 6-[ 18 F]fluoro-L-m-tyrosine imaging and motor performances analysis.
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