Age-related increase of alpha-synuclein oligomers is associated with motor disturbances in L61 transgenic mice.
Neurobiol Aging
; 101: 207-220, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33639338
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Envelhecimento
/
Corpos de Lewy
/
Alfa-Sinucleína
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Suécia