Age-related increase of alpha-synuclein oligomers is associated with motor disturbances in L61 transgenic mice

NEUROBIOLOGY OF AGING

卷:101

Article

Roshanbin, Sahar¹  Aniszewska, Agata¹  Gumucio, Astrid¹  Masliah, Eliezer²  Erlandsson, Anna¹  Bergstrom, Joakim¹  Ingelsson, Martin¹  Ekmark-Lewen, Sara¹ 

[1] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden

[2] NIA, Div Neurosci, NIH, Bethesda, MD 20892 USA

关键词: Parkinson's disease;    Dementia with Lewy bodies;    Alpha-synuclein;    Transgenic mice;    Sex differences;    Aggregation;    Oligomers;    Thy-1;    Age progression;   

DOI  :  10.1016/j.neurobiolaging.2021.01.010

来源: Elsevier

【 摘 要 】

The pathogenesis of Parkinson's disease involves fibrillization and deposition of alpha-synuclein (alpha-syn) into Lewy bodies. Accumulating evidence suggests that alpha-syn oligomers are particularly neurotoxic. Transgenic (tg) mice overexpressing wild-type human alpha-syn under the Thy-1 promoter (L61) reproduce many Parkinson's disease features, but the pathogenetic relevance of alpha-syn oligomers in this mouse model has not been studied in detail. Here, we report an age progressive increase of alpha-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 alpha-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 alpha-syn oligomers are central to the development of brain pathology and behavioral deficits in the L61 tg alpha-syn mouse model. (C) 2021 The Authors. Published by Elsevier Inc.

【 授权许可】

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