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Lactate Contributes to Ammonia-Mediated Astroglial Dysfunction During Hyperammonemia

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Abstract

Even though ammonia is considered to underlie nervous system symptoms of dysfunction during hyperammonemia, lactate, which increases as a metabolic consequence of high ammonia levels, might also be a contributing factor. The data presented here show that NH4Cl (5 mM) mediates astroglial cell swelling, and that treatment with NH4Cl or lactate (25 mM) causes rearrangements of actin filaments and reduces astroglial glutamate uptake capacity. Co-application with BaCl2, which blocks astroglial uptake of NH4 +, prevents NH4Cl-mediated cell swelling and rearrangement of actin filaments, but does not reduce NH4Cl-induced glutamate uptake capacity inhibition. Neither NH4Cl nor lactate affected glutamate uptake or protein expression in microglial cultures, indicating that astroglial cells are more susceptible to the neurotoxic affects of ammonia. Our results suggest that ammonium underlies brain edema, but that lactate can contribute to some of the cellular dysfunctions associated with elevated cerebral levels of ammonia.

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Acknowledgements

The skilful technical assistance of Ulrika Björklund, Mona Brantefjord, and Barbro Eriksson is greatly appreciated. The research was supported by the Swedish Research Council (Grant Nos. 33B1-14739, 33X-06812 and 2006–6385), the Swedish Society for Medical research, the Edith Jacobsson’s Foundation, the Royal Society of Arts and Sciences in Göteborg, Sweden, Folksam′s Research Foundation, and Arvid Carlsson’s Foundation.

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Authors and Affiliations

  1. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 19, 1 tr, Gothenburg, 413 45, Sweden

    Anna K. Andersson, Mikael Persson, Anna Westerlund & Elisabeth Hansson

  2. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden

    Louise Adermark

  3. Department of Signals and Systems, Chalmers University of Technology, Gothenburg, Sweden

    Torsten Olsson

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  1. Anna K. Andersson
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Correspondence to Elisabeth Hansson.

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Andersson, A.K., Adermark, L., Persson, M. et al. Lactate Contributes to Ammonia-Mediated Astroglial Dysfunction During Hyperammonemia. Neurochem Res 34, 556–565 (2009). https://doi.org/10.1007/s11064-008-9819-1

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