title: Vitamin E deficiency and metabolic deficits in neuronal ceroid lipofuscinosis described by bioinformatics.
abstract: The mnd mouse, a model of neuronal ceroid lipofusinosis (NCL), has a profound vitamin E deficiency in sera and brain, associated with cerebral deterioration characteristic of NCL. In this study, the vitamin E deficiency is corrected using dietary supplementation. However, the histopathological features associated with NCL remained. With use of a bioinformatics approach based on high-resolution solid and solution state 1H-NMR spectroscopy and principal component analysis (PCA), the deficits associated with NCL are defined in terms of a metabolic phenotype. Although vitamin E supplementation reversed some of the metabolic abnormalities, in particular the concentration of phenylalanine in extracts of cerebral tissue, PCA demonstrated that metabolic deficits associated with NCL were greater than any effects produced from vitamin E supplementation. These deficits included increased glutamate and N-acetyl-L-aspartate and decreased creatine and glutamine concentrations in aqueous extracts of the cortex, as well as profound accumulation of lipid in intact cerebral tissue. This is discussed in terms of faulty production of mitochondrial-associated membranes, thought to be central to the deficits in mnd mice.
authors.affiliation: Biological Chemistry, Biomedical Sciences, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW7 2AZ. jlg40@mole.bio.cam.uk
authors.forename: J L
authors.initials: JL
authors.lastname: Griffin
authors.forename: D
authors.initials: D
authors.lastname: Muller
authors.forename: R
authors.initials: R
authors.lastname: Woograsingh
authors.forename: V
authors.initials: V
authors.lastname: Jowatt
authors.forename: A
authors.initials: A
authors.lastname: Hindmarsh
authors.forename: J K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: J E
authors.initials: JE
authors.lastname: Martin
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D019587:Dietary Supplements; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009472:Neuronal Ceroid-Lipofuscinoses / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D025341:Principal Component Analysis; D014810:Vitamin E / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use; D014811:Vitamin E Deficiency / Q000378:metabolism* / Q000628:therapy
chemical_list: C498493:Cln8 protein, mouse; D008565:Membrane Proteins; D014810:Vitamin E