Preformed fibrils generated from mouse alpha-synuclein produce more inclusion pathology in rats than fibrils generated from rat alpha-synuclein.
Parkinsonism Relat Disord
; 89: 41-47, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34218047
ABSTRACT
BACKGROUND:
Alpha-synuclein (α-syn) preformed fibril (PFF)-induced pathology can be used to study the features and progression of synucleinopathies, such as Parkinson's disease. Intrastriatal injection of mouse α-syn PFFs produce accumulation of α-syn pathology in both mice and rats. Previous studies in mice have revealed that greater sequence homology between the α-syn amino acid sequence used to produce PFFs with that of the endogenous host α-syn increases α-syn pathology in vivo. NEWMETHODS:
Based on the prediction that greater sequence homology will result in more α-syn pathology, PFFs generated from recombinant rat α-syn (rPFFs) were used instead of PFFs produced from recombinant mouse α-syn (mPFFs), which are normally used in the model. Rats received unilateral intrastriatal injections of either rPFFs or mPFFs and accumulation of α-syn phosphorylated at serine 129 (pSyn) was examined at 1-month post-surgery.RESULTS:
Rats injected with mPFFs exhibited abundant accumulation of α-syn inclusions in the substantia nigra and cortical regions, whereas in rats injected with rPFFs had significantly fewer SNpc neurons containing pSyn inclusions (≈60% fewer) and little, if any, pSyn inclusions were observed in the cortex.CONCLUSIONS:
Our results suggest that additional factors beyond the degree of sequence homology between host α-syn and injected recombinant α-syn impact efficiency of seeding and subsequent inclusion formation. More practically, these findings caution against the use of rPFFs in the rat preformed fibril model.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Alfa-Sinucleína
/
Sinucleinopatias
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article