Lactate contributes to ammonia-mediated astroglial dysfunction during hyperammonemia.

Neurochemical Research
Anna K AnderssonE Hansson

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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Citations

Oct 13, 2011·Neurochemistry International·Kakulavarapu V Rama Rao, Michael D Norenberg
Jul 6, 2010·Neurochemistry International·Christopher F Rose
Jul 3, 2013·Nature Reviews. Gastroenterology & Hepatology·Roger F Butterworth
Oct 27, 2012·Metabolic Brain Disease·A R Jayakumar, M D Norenberg

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