Citrate, beneficial or deleterious in the CNS?
Cerebellar granule neurons were incubated with or without glucose (3 mM) in the presence or absence of citrate (20 mM) using normoxic and/or hypoxic incubation conditions. During 4 h of hypoglycemia and also during hypoxia plus hypoglycemia, citrate increased lactate dehydrogenase (LDH) leakage from the cells and decreased mitochondrial activity, the latter was also the case in the presence of glucose. After 24 h of hypoglycemia, however, citrate decreased LDH leakage slightly, possibly due to its metabolism in the tricarboxylic acid cycle under these conditions. It should be noted that during mild hypoxia plus hypoglycemia a reduced LDH leakage was observed when compared to hypoglycemia alone. The 4 h low oxygen period did protect the neurons also during the 20 h re-oxygenation period. The present study might indicate that incubation of brain cell cultures in an atmosphere of air (30% oxygen) and 5% CO2, which is used in most laboratories, can be toxic and that oxygen concentration should be lowered considerably to mimic conditions in the brain.
Sonnewald
Ursula
U
Department of Clinical Neuroscience, Medical Faculty, Norwegian University of Science and Technology, Trondheim. Ursula.Sonnewald@medisin.ntnu.no
Risan
Aksel Galtung
AG
Hole
Hans Bjørnar
HB
Westergaard
Niels
N
Qu
Hong
H
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology*; D002952:Citric Acid Cycle / Q000502:physiology; D004396:Coloring Agents; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012016:Reference Values; D013778:Tetrazolium Salts; D013844:Thiazoles
D002614:Chelating Agents; D002951:Citrates; D004396:Coloring Agents; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; D005947:Glucose