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MRS reveals additional hexose N ‐acetyl resonances in the brain of a mouse model for Sandhoff disease
Author(s) -
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.
Publication year - 2005
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.984
Subject(s) - sandhoff disease , neurodegeneration , biochemistry , chemistry , glycosphingolipid , biology , gene , disease , medicine
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. 1 H 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.