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Brain MR Imaging and Proton MR Spectroscopy in Female Mice with Pyruvate Dehydrogenase Complex Deficiency

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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.

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Acknowledgment

This study was supported in part by the National Organization for Rare Disorders (NORD).

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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Biomedical Sciences, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY, 14214, USA

    Lioudmila Pliss & Mulchand S. Patel

  2. Departments of Molecular and Cellular Biophysics and Diagnostic Imaging, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA

    Richard Mazurchuk & Joseph A. Spernyak

Authors
  1. Lioudmila Pliss
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  2. Richard Mazurchuk
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  3. Joseph A. Spernyak
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  4. Mulchand S. Patel
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Corresponding author

Correspondence to Mulchand S. Patel.

Additional information

Special issue dedicated to John P. Blass.

Lioudmila Pliss and Richard Mazurchuk are two investigators who contributed equally.

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Pliss, L., Mazurchuk, R., Spernyak, J.A. et al. Brain MR Imaging and Proton MR Spectroscopy in Female Mice with Pyruvate Dehydrogenase Complex Deficiency. Neurochem Res 32, 645–654 (2007). https://doi.org/10.1007/s11064-007-9295-z

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  • DOI: https://doi.org/10.1007/s11064-007-9295-z

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