Behavioural and dopaminergic changes in double mutated human A30P*A53T alpha-synuclein transgenic mouse model of Parkinson´s disease.

Show full item record



Permalink

http://hdl.handle.net/10138/307613

Citation

Kilpeläinen , T , Julku , U , Svarcbahs , R & Myöhänen , T 2019 , ' Behavioural and dopaminergic changes in double mutated human A30P*A53T alpha-synuclein transgenic mouse model of Parkinson´s disease. ' , Scientific Reports , vol. 9 , no. 1 , 17382 . https://doi.org/10.1038/s41598-019-54034-z

Title: Behavioural and dopaminergic changes in double mutated human A30P*A53T alpha-synuclein transgenic mouse model of Parkinson´s disease.
Author: Kilpeläinen, Tommi; Julku, Ulrika; Svarcbahs, Reinis; Myöhänen, Timo
Contributor: University of Helsinki, PREP in neurodegenerative disorders
University of Helsinki, Regenerative pharmacology group
University of Helsinki, Regenerative pharmacology group
University of Helsinki, Faculty of Pharmacy
Date: 2019-11-22
Language: eng
Number of pages: 13
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/307613
Abstract: Alpha-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 coding SNCA gene 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, whereas SNCA mutations 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.
Subject: AGE
AGGREGATION
ATTENUATION
HYPERACTIVITY
IN-VITRO
MICE
MOTOR
PATHOLOGY
PHOSPHORYLATION
TYROSINE-HYDROXYLASE
317 Pharmacy
1182 Biochemistry, cell and molecular biology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
s41598_019_54034_z.pdf 5.209Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record