Related Experiment Video
Updated: Jun 2, 2026
Bioluminescence Imaging of Neuroinflammation in Transgenic Mice After Peripheral Inoculation of Alpha-Synuclein Fibrils
Published on: April 13, 2017
Transmission of prion strains in a transgenic mouse model overexpressing human A53T mutated α-synuclein
Anne-Laure J Mougenot1, Anna Bencsik, Simon Nicot
1Agence Nationale de Sécurité Sanitaire de l'alimentation, de l'environnement et du travail - ANSES, Lyon, France.
Abstract:
There is a growing interest in the potential roles of misfolded protein interactions in neurodegeneration. To investigate this issue, we inoculated 3 prion strains intracerebrally into transgenic (TgM83) mice that overexpress human A53T α-synuclein. In comparison to nontransgenic controls, there was a striking decrease in the incubation periods of scrapie, classic and H-type bovine spongiform encephalopathies(C-BSE and H-BSE), with conservation of the histopathologic and biochemical features characterizing these 3 prion strains. TgM83 mice died of scrapie or C-BSE prion diseases before accumulating the insoluble and phosphorylated forms of α-synuclein specific to late stages of synucleinopathy. In contrast, the median incubation time for TgM83 mice inoculated with H-BSE was comparable to that observed when these mice were uninfected, thereby allowing the development of molecular alterations of α-synuclein. The last 4 mice of this cohort exhibited early accumulations of H-BSE prion protein along with α-synuclein pathology. The results indicate that a prion disease was triggered concomitantly with an overt synucleinopathy in some transgenic mice overexpressing human A53T α-synuclein after intracerebral inoculation with an H-BSE prion strain.
Insights
Prion diseases accelerated neurodegeneration in mice overexpressing human alpha-synuclein. H-type BSE triggered both prion disease and alpha-synuclein pathology, suggesting a link between misfolded proteins in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Protein misfolding diseases
- Transmissible spongiform encephalopathies
Background:
- Growing interest in misfolded protein interactions in neurodegeneration.
- Transgenic (TgM83) mice overexpress human A53T α-synuclein.
- Investigating prion strain effects on α-synucleinopathy.
Purpose of the Study:
- To investigate the impact of prion strains on A53T α-synucleinopathy.
- To determine if prion infection alters the course of α-synuclein accumulation.
- To explore the interplay between prion diseases and synucleinopathies.
Main Methods:
- Intracerebral inoculation of 3 prion strains (scrapie, C-BSE, H-BSE) into TgM83 mice.
- Comparison with nontransgenic controls.
- Histopathological and biochemical analysis of prion and α-synuclein pathology.
Main Results:
- Scrapie and C-BSE shortened incubation periods but did not induce α-synuclein pathology before death.
- H-BSE inoculation allowed α-synuclein alterations to develop.
- Some H-BSE inoculated mice showed concomitant prion and α-synuclein pathology.
Conclusions:
- Prion diseases can influence the progression of α-synucleinopathies.
- H-BSE prion strain can trigger both prion disease and synucleinopathy in TgM83 mice.
- Suggests a potential link between prion diseases and α-synuclein misfolding in neurodegeneration.
More Related Videos
12:01Detection of Disease-associated α-synuclein by Enhanced ELISA in the Brain of Transgenic Mice Overexpressing Human A53T Mutated α-synuclein
Published on: May 30, 2015
09:16Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
Published on: June 26, 2018