Related Experiment Videos
Metabolic changes associated with vacuolation in murine models of scrapie using in vitro 1H-NMR spectroscopy
Y L Chung1, A Williams, A Chong
1Robert Steiner MR Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Abstract:
In this study, metabolic changes in the 79A/C3H, ME7/VM, ME7/C3H, 87V/VM and 22A/SV scrapie mouse models were investigated during the clinical phase of the disease, using in vitro proton nuclear magnetic resonance spectroscopy. N-acetyl-aspartate was found to be significantly reduced in infected mice of the ME7/ C3H (40% reduction), ME7/VM (26%) and 79A/C3H (17%) models when compared to control mice, but not in the 87V/VM and 22A/SV models. The concentration of choline containing compounds and creatine remain unchanged in all models when compared with control murine brains. The level of N-acetyl-aspartate reduction correlated with the extent of grey-matter brain vacuolation. The levels of myo-inositol were found to be significantly increased in the ME7/VM (143%) and 79A/C3H (132%) models only and no significant changes were observed in the ME7/C3H, 87V/VM and 22A/SV models. These changes did not correspond to the severity of gliosis.
Insights
Metabolic changes in scrapie mouse models reveal reduced N-acetyl-aspartate in infected brains, correlating with grey matter vacuolation. Choline and creatine levels remained stable, while myo-inositol increased in specific models.
Area of Science:
- Neuroscience
- Biochemistry
- Veterinary Medicine
Background:
- Scrapie is a fatal neurodegenerative prion disease affecting sheep and goats.
- Understanding metabolic alterations in scrapie mouse models is crucial for disease mechanism research.
- The clinical phase of scrapie is characterized by progressive neurological dysfunction.
Purpose of the Study:
- To investigate metabolic changes in various scrapie mouse models during the clinical disease phase.
- To identify specific metabolites altered by scrapie infection using in vitro proton nuclear magnetic resonance spectroscopy.
- To correlate metabolic changes with neuropathological findings like vacuolation and gliosis.
Main Methods:
- Utilized in vitro proton nuclear magnetic resonance spectroscopy (1H-NMRS).
- Analyzed brain tissue from five distinct scrapie mouse models (79A/C3H, ME7/VM, ME7/C3H, 87V/VM, 22A/SV) during the clinical phase.
- Compared metabolite concentrations in infected mice against control groups.
Main Results:
- Significant reduction in N-acetyl-aspartate (NAA) observed in ME7/C3H, ME7/VM, and 79A/C3H models.
- NAA reduction correlated with the extent of grey matter vacuolation.
- Increased myo-inositol levels detected in ME7/VM and 79A/C3H models.
- Choline-containing compounds and creatine levels remained unchanged across all models.
- Metabolic changes did not correlate with the severity of observed gliosis.
Conclusions:
- Scrapie infection induces specific metabolic alterations in susceptible mouse models.
- N-acetyl-aspartate reduction is a key metabolic hallmark associated with neuropathological damage in certain scrapie strains.
- Myo-inositol alterations may indicate specific cellular responses or disease progression pathways in some models.
- Metabolic profiling provides insights into the pathophysiology of prion diseases.