Age-related increase of alpha-synuclein oligomers is associated with motor disturbances in L61 transgenic mice
Sahar Roshanbin, Agata Aniszewska, Astrid Gumucio, Eliezer Masliah, Anna Erlandsson, Joakim Bergström, Martin Ingelsson, Sara Ekmark‐Lewén
Abstract
The pathogenesis of Parkinson's disease involves fibrillization and deposition of alpha-synuclein (α-syn) into Lewy bodies. Accumulating evidence suggests that α-syn oligomers are particularly neurotoxic. Transgenic (tg) mice overexpressing wild-type human α-syn under the Thy-1 promoter (L61) reproduce many Parkinson's disease features, but the pathogenetic relevance of α-syn oligomers in this mouse model has not been studied in detail. Here, we report an age progressive increase of α-syn oligomers in the brain of L61 tg mice. Interestingly, more profound motor symptoms were observed in animals with higher levels of membrane-bound oligomers. As this tg model is X-linked, we also performed subset analyses, indicating that both sexes display a similar age-related increase in α-syn oligomers. However, compared with females, males featured increased brain levels of oligomers from an earlier age, in addition to a more severe behavioral phenotype with hyperactivity and thigmotaxis in the open field test. Taken together, our data indicate that α-syn oligomers are central to the development of brain pathology and behavioral deficits in the L61 tg α-syn mouse model.