HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 11/3/195    most recent 00100.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Griffin, J. L. Articles by Martin, J. E. Search for Related Content PubMed PubMed Citation Articles by Griffin, J. L. Articles by Martin, J. E.

Vitamin E deficiency and metabolic deficits in neuronal ceroid lipofuscinosis described by bioinformatics

¹ Biological Chemistry, Biomedical Sciences, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW7 2AZ
² Histopathology, Barts and the London, Queen Mary’s School of Medicine and Dentistry, The Royal London Hospital, Whitechapel, London E1 1BB
³ Institute of Child Health, London WC1 N1EH, United Kingdom

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.

Batten’s disease; motor neuron degeneration; metabolic profile; metabotype; neuronal ceroid lipofuscinosis; vitamin E

This article has been cited by other articles:

				M. R. Pears, J. D. Cooper, H. M. Mitchison, R. J. Mortishire-Smith, D. A. Pearce, and J. L. Griffin High Resolution 1H NMR-based Metabolomics Indicates a Neurotransmitter Cycling Deficit in Cerebral Tissue from a Mouse Model of Batten Disease J. Biol. Chem., December 30, 2005; 280(52): 42508 - 42514. [Abstract] [Full Text] [PDF]

				J. L. Griffin, C. K. Cemal, and M. A. Pook Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3 Physiol Genomics, February 13, 2004; 16(3): 334 - 340. [Abstract] [Full Text] [PDF]

				I. Jarvela and S. B. Glueck Charting the effects of antioxidant therapy in the diseased brain: Focus on "Vitamin E deficiency and metabolic deficits in neuronal ceroid lipofuscinosis described by bioinformatics" Physiol Genomics, December 3, 2002; 11(3): 183 - 184. [Full Text] [PDF]