Lactate contributes to ammonia-mediated astroglial dysfunction during hyperammonemia.
Artikel i vetenskaplig tidskrift, 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
Författare
Anna Andersson
Göteborgs universitet
Louise Adermark
Göteborgs universitet
Mikael Persson
Göteborgs universitet
Anna Westerlund
Göteborgs universitet
Torsten Olsson
Chalmers, Signaler och system, Signalbehandling och medicinsk teknik
Elisabeth Hansson
Göteborgs universitet
Neurochemical Research
0364-3190 (ISSN) 1573-6903 (eISSN)
Vol. 34 3 556-65Ämneskategorier (SSIF 2011)
Neurovetenskaper
Farmakologi och toxikologi
DOI
10.1007/s11064-008-9819-1
PubMed
18716864