Title: Longitudinal follow-up and characterization of a robust rat model for Parkinson's disease based on overexpression of alpha-synuclein with adeno-associated viral vectors
Authors: Van der Perren, Anke
Toelen, Jaan
Casteels, Cindy
Macchi, Francesca
Van Rompuy, Anne-Sophie
Sarre, Sophie
Casadei, Nicolas
Nuber, Silke
Himmelreich, Uwe
Osorio Garcia, Maria Isabel
Michotte, Yvette
D'Hooge, Rudi
Bormans, Guy
Van Laere, Koen
Gijsbers, Rik
Van Den Haute, Chris
Debyser, Zeger
Baekelandt, Veerle # ×
Issue Date: Mar-2015
Publisher: Elsevier
Series Title: Neurobiology of Aging vol:36 issue:3 pages:1543-58
Article number: S0197-4580(14)00786-6
Abstract: Testing of new therapeutic strategies for Parkinson's disease (PD) is currently hampered by the lack of relevant and reproducible animal models. Here, we developed a robust rat model for PD by injection of adeno-associated viral vectors (rAAV2/7) encoding α-synuclein into the substantia nigra, resulting in reproducible nigrostriatal pathology and behavioral deficits in a 4-week time period. Progressive dopaminergic dysfunction was corroborated by histopathologic and biochemical analysis, motor behavior testing and in vivo microdialysis. L-DOPA treatment was found to reverse the behavioral phenotype. Non-invasive positron emission tomography imaging and magnetic resonance spectroscopy allowed longitudinal monitoring of neurodegeneration. In addition, insoluble α-synuclein aggregates were formed in this model. This α-synuclein rat model shows improved face and predictive validity, and therefore offers the possibility to reliably test novel therapeutics. Furthermore, it will be of great value for further research into the molecular pathogenesis of PD and the importance of α-synuclein aggregation in the disease process.
ISSN: 0197-4580
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group for Neurobiology and Gene Therapy
Organ Systems (+)
Nuclear Medicine & Molecular Imaging
Biomedical MRI
Laboratory for Biological Psychology
Radiopharmaceutical Research
Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

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