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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9648497 | PMC |
| http://dx.doi.org/10.1016/j.neurobiolaging.2021.01.010 | DOI Listing |
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