Lactate contributes to ammonia-mediated astroglial dysfunction during hyperammonemia.
Journal article, 2009

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.

Calcium

ultrastructure

metabolism

pathology

Excitatory Amino Acid Transporter 1

Microfilaments

pharmacology

metabolism

pathology

metabolism

pharmacology

Cultured

Neurons

Rats

Excitatory Amino Acid Transporter 2

Lactic Acid

biosynthesis

metabolism

metabolism

Coculture Techniques

Animals

Astrocytes

biosynthesis

Sprague-Dawley

Cell Size

Hyperammonemia

Ammonium Chloride

metabolism

Rats

Ammonia

pathology

Cells

Author

Anna Andersson

University of Gothenburg

Louise Adermark

University of Gothenburg

Mikael Persson

University of Gothenburg

Anna Westerlund

University of Gothenburg

Torsten Olsson

Chalmers, Signals and Systems, Signalbehandling och medicinsk teknik, Biomedical Signals and Systems

Elisabeth Hansson

University of Gothenburg

Neurochemical Research

0364-3190 (ISSN) 1573-6903 (eISSN)

Vol. 34 3 556-65

Subject Categories

Neurosciences

Pharmacology and Toxicology

DOI

10.1007/s11064-008-9819-1

PubMed

18716864

More information

Created

10/7/2017