title: Brain MR imaging and proton MR spectroscopy in female mice with pyruvate dehydrogenase complex deficiency.
abstract: Pyruvate dehydrogenase complex (PDC) deficiency is an inborn metabolic disorder that causes neurological abnormalities. In this report, a murine model of PDC deficiency was analyzed using histology, magnetic resonance (MR) imaging and MR spectroscopy (MRS) and the results compared to PDC-deficient female patients. Histological analysis of brains from PDC-deficient mice revealed defects in neuronal cytoarchitecture in grey matter and reduced size of white matter structures. MR results were comparable to previously published clinical MR findings obtained from PDC-deficient female patients. Specifically, a 15.4% increase in relative lactate concentration, 64.4% loss of N-acetylaspartate concentration and a near complete loss of discernable glutamine plus glutamate concentration were observed in a PDC deficient mouse compared to wild-type control. Lower apparent diffusion coefficients (ADCs) were observed within the brain consistent with atrophy. These results demonstrate the usefulness of this murine model to systematically evaluate the beneficial effects of dietary and pharmacological interventions.
authors.affiliation: Department of Biochemistry, School of Medicine, Biomedical Sciences, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Lioudmila
authors.initials: L
authors.lastname: Pliss
authors.forename: Richard
authors.initials: R
authors.lastname: Mazurchuk
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Spernyak
authors.forename: Mulchand S
authors.initials: MS
authors.lastname: Patel
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000002:abnormalities / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005091:Exons; D005260:Female; D007091:Image Processing, Computer-Assisted; D007381:Intermediate Filament Proteins / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008279:Magnetic Resonance Imaging; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000378:metabolism* / Q000473:pathology*; D051381:Rats
chemical_list: D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D011768:Pyruvate Dehydrogenase Complex