Mapping alteration of dopaminergic neurons in a rat model of Parkinson Disease through the comparison of the presynaptic PET tracers

Autor: Roost, Pauline, Gubinelli, Francesco, Gaudin, Mylène, Guillermier, Martine, Cresto, Noémie, Eymin, Leopold, Josephine, Charlène, Gaillard, Marie-Claude, Bemelmans, Alexis, Bramoullé, Yann, Brouillet, Emmanuel, Hantraye, Philippe, Van Camp, Nadja
Rok vydání: 2018
Předmět:
Zdroj: Network for European CNS Transplantation and Restoration Meeting (NECTAR2018), Paris, France, December 2018
ISSN: 0896-6273
DOI: 10.5281/zenodo.2417607
Popis: NECTAR 2018 Parkinson’s Disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra (SN) resulting in a dopamine deficiency in the striatum.1 We developed a pathologically relevant rat model of PD using viral vectors to overexpress mutant alpha-synuclein.2 Our aims were to evaluate the dopaminergic changes and neuronal loss at different time-points in this model with two different presynaptic PET tracers, and relate imaging results with behavioural and histological changes. Therefor rats were unilaterally injected in the SN with AAV2/6 viral vector coding for mutated (A53T) human alpha-synuclein, and were studied at 6 or 12 weeks post-injection (wpi). PET imaging was performed using 6-[18F]fluoro-L-m-tyrosine3 (FMT), a substrate for AADC and [18F]-LBT9994 (LBT), a radioligand for dopamine transporter (DAT). Quantitative uptake images were calculated using Logan and Patlak graphical methods, with a cerebellar reference. At 6wpi we did not observe any asymmetry in the striatum; neither with FMT (n=5;p=0.421) nor LBT (n=6;p=0.310). At 12wpi we observed an asymmetry with LBT (n=4;p=0.003), but not with FMT (n=2;p=0.336). Histological evaluation showed 28% loss of TH-positive cells in the SN at 12wpi (n=8;p=0.031), but not at 6wpi (n=6;ns). A motor deficit was observed with the cylinder test at both time-points (n=7/8;pin vivo in a rat model characterized by progressive and mild neurodegeneration of the nigro-striatal pathway. This PET tracer may be of particular interest to test neuroprotective or neuro-restorative therapeutic strategies in future studies using our PD rat model. References: 1. [10.1016/S0896-6273(03)00568-3] 2. Cresto et al. [2017], Neurodegener Dis 2017;17(suppl 1):8-590 – Page 448. 3. [10.1111/jnc.14016] 4. [10.1016/j.nucmedbio.2013.09.007] Acknowledgements: This project has been funded by the European Union Horizon 2020 Programme (H2020-MSCA-ITN-2015) under the Marie Skłodowska-Curie Innovative Training Network and Grant Agreement No.676408.
This project has been funded by the European Union Horizon 2020 Programme (H2020-MSCA-ITN-2015) under the Marie Skłodowska-Curie Innovative Training Network and Grant Agreement No.676408.
Databáze: OpenAIRE
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