Neurobiology of Aging 2015-03-01

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.

Anke Van der Perren, Jaan Toelen, Cindy Casteels, Francesca Macchi, Anne-Sophie Van Rompuy, Sophie Sarre, Nicolas Casadei, Silke Nuber, Uwe Himmelreich, Maria Isabel Osorio Garcia, Yvette Michotte, Rudi D'Hooge, Guy Bormans, Koen Van Laere, Rik Gijsbers, Chris Van den Haute, Zeger Debyser, Veerle Baekelandt

Index: Neurobiol. Aging 36 , 1543-58, (2015)

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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.Copyright © 2015 Elsevier Inc. All rights reserved.