MRS reveals additional hexose N-acetyl resonances in the brain of a mouse model for Sandhoff disease

Sandhoff disease, one of several related lysosomal storage disorders, results from the build up of N‐acetyl‐containing glycosphingolipids in the brain and is caused by mutations in the genes encoding the hexosaminidase β‐subunit. Affected individuals undergo progressive neurodegeneration in response...

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Bibliographic Details
Published in:NMR in biomedicine 2005-12, Vol.18 (8), p.517-526
Main Authors: Lowe, J. P., Stuckey, D. J., Awan, F. R., Jeyakumar, M., Neville, D. C. A., Platt, F. M., Griffin, J. L., Styles, P., Blamire, A. M., Sibson, N. R.
Format: Article
Language:English
Subjects:
Animals
Carbohydrate Conformation
Carbohydrate Sequence
Disease Models, Animal
Disease Progression
glycosphingolipids
Hexoses - chemistry
Humans
magic angle spinning
Magnetic Resonance Spectroscopy
mass spectrometry
Mice
Mice, Inbred C57BL
Molecular Sequence Data
oligosaccharide
Oligosaccharides - chemistry
Sandhoff disease
Sandhoff Disease - metabolism
Sandhoff Disease - physiopathology
Tissue Extracts - chemistry
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Summary:Sandhoff disease, one of several related lysosomal storage disorders, results from the build up of N‐acetyl‐containing glycosphingolipids in the brain and is caused by mutations in the genes encoding the hexosaminidase β‐subunit. Affected individuals undergo progressive neurodegeneration in response to the glycosphingolipid storage. 1H magnetic resonance spectra of perchloric acid extracts of Sandhoff mouse brain exhibited several resonances ca 2.07 ppm that were not present in the corresponding spectra from extracts of wild‐type mouse brain. High‐performance liquid chromatography and mass spectrometry of the Sandhoff extracts post‐MRS identified the presence of N‐acetylhexosamine‐containing oligosaccharides, which are the likely cause of the additional MRS resonances. MRS of intact brain tissue with magic angle spinning also showed additional resonances at ca 2.07 ppm in the Sandhoff case. These resonances appeared to increase with disease progression and probably arise, for the most part, from the stored glycosphingolipids, which are absent in the aqueous extracts. Hence in vivo MRS may be a useful tool for detecting early‐stage Sandhoff disease and response to treatment. Copyright © 2005 John Wiley & Sons, Ltd.
ISSN:0952-3480
1099-1492
DOI:10.1002/nbm.984