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A Metabolomic Study of Brain Tissues from Aged Mice with Low Expression of the Vesicular Monoamine Transporter 2 (VMAT2) Gene

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Abstract

The vesicular monoamine transporter 2 (VMAT2) sequesters monoamines into synaptic vesicles in preparation for neurotransmission. Samples of cerebellum, cortex, hippocampus, substantia nigra and striatum from VMAT2-deficient mice were compared to age-matched control mice. Multivariate statistical analyses of 1H NMR spectral profiles separated VMAT2-deficient mice from controls for all five brain regions. Although the data show that metabolic alterations are region- and age-specific, in general, analyses indicated decreases in the concentrations of taurine and creatine/phosphocreatine and increases in glutamate and N-acetyl aspartate in VMAT2-deficient mouse brain tissues. This study demonstrates the efficacy of metabolomics as a functional genomics phenotyping tool for mouse models of neurological disorders, and indicates that mild reductions in the expression of VMAT2 affect normal brain metabolism.

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Acknowledgements

This work was supported by the NIH grant R21 DK070288-01, USA (RMS), The Royal Society, UK (a University Research Fellowship to JLG), the UK Parkinson’s Disease Society (Grant No 4039) and the BBSRC (PCE and PJL). REC was supported by an MRC case studentship with Sanofi-Aventis.

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Authors and Affiliations

  1. Department of Biochemistry, University of Cambridge, Hopkins building, Building O, Downing Site, Tennis Court Road, Cambridge, CB2 1QW, UK

    Reza M. Salek, Robin Macintosh & Julian L. Griffin

  2. Laboratory of Molecular Neuroscience, The Babraham Institute, Babraham, Cambridge, CB22 3AT, UK

    Rebecca E. Colebrooke, Patrick J. Lynch & Piers C. Emson

  3. Safety Assessment, GlaxoSmithKline, Park Road, Ware, Herts, SG12 ODP, UK

    Brian C. Sweatman

Authors
  1. Reza M. Salek
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  2. Rebecca E. Colebrooke
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  3. Robin Macintosh
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  4. Patrick J. Lynch
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  5. Brian C. Sweatman
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  6. Piers C. Emson
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  7. Julian L. Griffin
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Correspondence to Julian L. Griffin.

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Special issue article in honor of Dr. Frode Fonnum.

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Salek, R.M., Colebrooke, R.E., Macintosh, R. et al. A Metabolomic Study of Brain Tissues from Aged Mice with Low Expression of the Vesicular Monoamine Transporter 2 (VMAT2) Gene. Neurochem Res 33, 292–300 (2008). https://doi.org/10.1007/s11064-007-9542-3

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  • DOI: https://doi.org/10.1007/s11064-007-9542-3

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