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Published on: August 31, 2010
Brain bioenergetics in murine models of scrapie using in vivo 31P magnetic resonance spectroscopy
Y L Chung1, S C Williams, J Hope
1Robert Steiner MR Unit, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Abstract:
The bioenergetic status of the brain in scrapie mouse models was investigated during the late, clinical phase of the disease, by in vivo phosphorus magnetic resonance spectroscopy (MRS). The only significant change observed in the scrapie-infected mice compared with controls was an increase in intracellular brain pH (7.20+/-0.06 vs 7.10+/-0.05). No other changes in energetic metabolism were observed in the infected mice beside a trend in the decrease of phosphomonoester (PME) level, possibly associated with an alteration in glycolytic intermediates. This study showed that even in the presence of severe cellular vacuolation and microglia infiltrate, cerebral bioenergetic is maintained.
Insights
Brain bioenergetics remain stable in scrapie mouse models, even with severe cellular changes. Researchers observed a slight increase in intracellular brain pH but no other significant metabolic alterations during the clinical disease phase.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Scrapie is a fatal neurodegenerative disease.
- Understanding brain bioenergetics is crucial for neurodegenerative disease research.
- Previous studies have not fully elucidated the bioenergetic status during the clinical phase of scrapie.
Purpose of the Study:
- To investigate the brain's bioenergetic status in a mouse model of scrapie during the late clinical phase.
- To identify specific metabolic changes associated with scrapie progression using in vivo phosphorus magnetic resonance spectroscopy (MRS).
Main Methods:
- In vivo phosphorus magnetic resonance spectroscopy (MRS) was employed.
- Scrapie mouse models were analyzed during the late, clinical stage of the disease.
- Brain pH and levels of key metabolites (e.g., phosphomonoester) were measured and compared to control groups.
Main Results:
- The primary significant finding was an increase in intracellular brain pH in scrapie-infected mice (7.20±0.06) compared to controls (7.10±0.05).
- No other significant alterations in cerebral energy metabolism were detected.
- A trend towards decreased phosphomonoester (PME) levels was observed, potentially indicating altered glycolytic intermediates.
Conclusions:
- Cerebral bioenergetic status is largely maintained despite severe neuropathological changes like cellular vacuolation and microglia infiltration in scrapie.
- The observed increase in brain pH may be an adaptive response or a consequence of altered cellular function in scrapie.
- Further research is needed to explore the implications of altered glycolytic intermediates and pH changes in scrapie pathogenesis.
