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A Comparison of Some Metabolic Effects of N-Methylaspartate Stereoisomers, Glutamate and Depolarization: A Multinuclear MRS Study

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Abstract

Exposure of guinea pig brain slices to low concentrations (10 μM) of NMDA caused decreases in PCr and ATP within 30 min, with a slower decrease in NAA and increase in lactate, both detectable after 1 h. Exposure to NMDA for over 1 h or at higher concentrations caused further increases in lactate and decreases in NAA, with no further change in PCr or ATP. The L-isomer, NMLA, and the racemic mixture, NMDLA, caused similar changes in lactate and NAA, but both produced greater decreases in the energy state than NMDA, similar to those caused by prolonged exposure to glutamate. MK-801 prevented the changes in the energy state caused by NMDA, but not those caused by NMLA or by glutamate. The results are compared to previous studies on depolarization and discussed in terms of the role of the NMDA sub-type of glutamate receptor in the excitotoxic hypothesis of neuronal degeneration.

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Authors and Affiliations

  1. M. R. Centre, School of Physics & Astronomy, University of Nottingham, Nottingham, NG7 2RD, U.K.

    N. M. Thatcher, R. S. Badar-Goffer, O. Ben-Yoseph, M. A. McLean, P. G. Morris, M. J. W. Prior, A. Taylor & H. S. Bachelard

  2. Pfizer Limited, Sandwich, Kent, CT13 9NJ

    N. M. Thatcher

  3. Philips Medical Systems NL bv, P.O. Box 10000, 5680 DA, Best, The Netherlands

    R. S. Badar-Goffer

  4. Ester Neurosciences Ltd., 2 Koifman Street, Tel-Aviv, 68012, Israel

    O. Ben-Yoseph

  5. National Society for Epilepsy, Chalfont St. Peter, Bucks, SL9 ORJ

    M. A. McLean

  6. Prutech, London, NW1 2PQ

    A. Taylor

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  1. N. M. Thatcher
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  3. O. Ben-Yoseph
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  8. H. S. Bachelard
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Thatcher, N.M., Badar-Goffer, R.S., Ben-Yoseph, O. et al. A Comparison of Some Metabolic Effects of N-Methylaspartate Stereoisomers, Glutamate and Depolarization: A Multinuclear MRS Study. Neurochem Res 27, 51–58 (2002). https://doi.org/10.1023/A:1014898421330

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  • DOI: https://doi.org/10.1023/A:1014898421330

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