title: MRS reveals additional hexose N-acetyl resonances in the brain of a mouse model for Sandhoff disease.
abstract: 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 beta-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.
authors.affiliation: Experimental Neuroimaging Group, University Laboratory of Physiology, University of Oxford, Parks Road, Oxford, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Lowe
authors.forename: D J
authors.initials: DJ
authors.lastname: Stuckey
authors.forename: F R
authors.initials: FR
authors.lastname: Awan
authors.forename: M
authors.initials: M
authors.lastname: Jeyakumar
authors.forename: D C A
authors.initials: DC
authors.lastname: Neville
authors.forename: F M
authors.initials: FM
authors.lastname: Platt
authors.forename: J L
authors.initials: JL
authors.lastname: Griffin
authors.forename: P
authors.initials: P
authors.lastname: Styles
authors.forename: A M
authors.initials: AM
authors.lastname: Blamire
authors.forename: N R
authors.initials: NR
authors.lastname: Sibson
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D018450:Disease Progression; D006601:Hexoses / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry; D012497:Sandhoff Disease / Q000378:metabolism* / Q000503:physiopathology; D014020:Tissue Extracts / Q000737:chemistry
chemical_list: D006601:Hexoses; D009844:Oligosaccharides; D014020:Tissue Extracts