Abstract
Top of pageAbstract Recombinant adeno-associated viral (rAAV) vector-mediated overexpression of |[alpha]|-synuclein (|[alpha]|Syn) protein has been shown to cause neurodegeneration of nigrostriatal dopaminergic pathway in rodents and primates. Using the serotype-2 rAAV vectors, we have recently reported the protective effect of Parkin on the |[alpha]|Syn-induced nigral dopaminergic neurodegeneration in a rat model. Here we investigated the neuronal specificity of |[alpha]|Syn toxicity and the effect of Parkin co-expression in a primate model. The serotype-1 rAAV (rAAV1) carrying |[alpha]|Syn cDNA (rAAV1-|[alpha]|Syn), and a cocktail of rAAV1-|[alpha]|Syn and rAAV1 carrying parkin cDNA (rAAV1-parkin) were unilaterally injected into the striatum of macaque monkeys, resulting in protein expression in striatonigral GABAergic and nigrostriatal dopaminergic neurons. The injection of rAAV1-|[alpha]|Syn alone caused a decrease of tyrosine hydroxylase- immunoreactivity in the striatum when compared to the contralateral side injected with a cocktail of rAAV1-|[alpha]|Syn and rAAV1-parkin. The immunostaining of the striatonigral GABAergic neurons showed no differences on each side. In the presence of overexpressed Parkin, |[alpha]|Syn protein seemed to be less accumulated and/or phosphorylated at Ser129 residue in GABAergic neurons. These results suggest that the toxicity of accumulated |[alpha]|Syn is not expressed in non- dopaminergic neurons but the |[alpha]|Syn-ablating effect of Parkin is exerted in all neurons introduced in primates.
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