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Media type:
E-Article
Title:
Behavioural and dopaminergic changes in double mutated human A30P*A53T alpha-synuclein transgenic mouse model of Parkinson´s disease
Contributor:
Kilpeläinen, Tommi;
Julku, Ulrika H.;
Svarcbahs, Reinis;
Myöhänen, Timo T.
Published:
Springer Science and Business Media LLC, 2019
Published in:
Scientific Reports, 9 (2019) 1
Language:
English
DOI:
10.1038/s41598-019-54034-z
ISSN:
2045-2322
Origination:
Footnote:
Description:
AbstractAlpha-synuclein (aSyn) is the main component of Lewy bodies, the histopathological marker in Parkinson’s disease (PD), and point mutations and multiplications of the aSyn codingSNCAgene correlate with early onset PD. Therefore, various transgenic mouse models overexpressing native or point-mutated aSyn have been developed. Although these models show highly increased aSyn expression they rarely capture dopaminergic cell loss and show a behavioural phenotype only at old age, whereasSNCAmutations are risk factors for PD with earlier onset. The aim of our study was to re-characterize a transgenic mouse strain carrying both A30P and A53T mutated human aSyn. Our study revealed decreased locomotor activity for homozygous transgenic mice starting from 3 months of age which was different from previous studies with this mouse strain that had behavioural deficits starting only after 7–9 months. Additionally, we found a decreased amphetamine response in locomotor activity and decreased extracellular dopaminergic markers in the striatum and substantia nigra with significantly elevated levels of aSyn oligomers. In conclusion, homozygous transgenic A30P*A53T aSyn mice capture several phenotypes of PD with early onset and could be a useful tool for aSyn studies.