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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

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

Neurobiology of aging, 2015-03, Vol.36 (3), p.1543-1558 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
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
Autor: 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
Assuntos: Adeno-associated viral vectors ; alpha-Synuclein - administration & dosage ; alpha-Synuclein - genetics ; alpha-Synuclein - metabolism ; Animal model ; Animals ; Behavior, Animal ; Dependovirus - genetics ; Disease Models, Animal ; Disease Progression ; Dopamine - metabolism ; Gene Expression ; Genetic Vectors - genetics ; Internal Medicine ; Longitudinal Studies ; Microdialysis ; Neurology ; Parkinson Disease - genetics ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Parkinson Disease - psychology ; Parkinson's disease ; PET imaging ; Positron-Emission Tomography ; Protein Aggregates ; Substantia Nigra - pathology ; Time Factors ; α-Synuclein
É parte de: Neurobiology of aging, 2015-03, Vol.36 (3), p.1543-1558
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Descrição: 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.
Editor: United States: Elsevier Inc
Idioma: Inglês

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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

United States: Elsevier Inc

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