Details

Autor(en) / Beteiligte

• Becker, Guillaume
• Michel, Anne
• Bahri, Mohamed Ali
• Mairet-Coello, Georges
• Lemaire, Christian
• Deprez, Tania
• Freyssin, Aline
• Jacquin, Lucas
• Hustadt, Fabian
• De Wolf, Catherine
• Caruso, Mélina
• Frequin, Jean-Marie
• Gillent, Eric
• Bezard, Erwan
• Garraux, Gaetan
• Luxen, André
• Citron, Martin
• Downey, Patrick
• Plenevaux, Alain

Titel

Monitoring of a progressive functional dopaminergic deficit in the A53T-AAV synuclein rats by combining 6-[18F]fluoro-L-m-tyrosine imaging and motor performances analysis

Ist Teil von

• Neurobiology of aging, 2021-11, Vol.107, p.142-152

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• •Development of α-synuclein aggregates accumulation in A53T-AAV α-syn rats.•Gradual deterioration of the dopaminergic function and activity in α-syn rats.•Progressive [18F]FMT Positron Emission Tomography signal reduction in the caudate putamen in α-syn rats.•Positive correlation between the [18F]FMT Positron Emission Tomography signal and motor behavior. 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 [18F]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 [18F]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.