Objective: Targeted over-expression of human α-synuclein using viral-vector mediated gene delivery into the substantia nigra of rats and non-human primates has been reported to lead to dopaminergic cell loss and the formation of α-synuclein aggregates reminiscent of Lewy bodies.

Background: In the context of these findings, we further validate long term functional and motor deficits in AAV-mediated α-synuclein transfection model in rats during chronic follow-up period.

Methods: Recombinant AAV expressing human α-synuclein (A53T) was stereotaxically injected unilaterally into substantia nigra of Wistar rats. Rats were allowed to recover for 3 weeks prior to initial baseline behavioral testing with rotational asymmetry test, stepping test and cylinder test. Similar behavioral test battery was applied again at weeks 5, 8 and 12. In addition to traditionally used rat PD model tests, MotoRater test system, a high speed kinematic motor performance monitoring was applied at multiple time-points during the follow-up period. Evaluation focused on animal gait, swimming, wading and ladder climbing between groups. Furthermore, integrity of the dopamine active transport (DAT) system was evaluated by using 123I- β-CIT and SPECT/CT imaging on weeks 3, 8 and 12 after AAV- α-synuclein transfection.

Results: This study focused on the validation of previously published AAV- α-synuclein transfection model in rats but with the addition of novel end-points.

Conclusions: We describe the long term phenotype of AAV- α-synuclein transfected rats with traditionally used behavioral tests but also by using novel fine motor analysis techniques and DAT imaging which provide new insight to uni- and bilateral effects of AAV α-synuclein transfection.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/targeted-over-expression-with-aav-mediated-human-synuclein-in-a-rat-model-of-parkinsons-disease-validation-of-novel-fine-motor-functional-effects/