title: Deoxyglucose prevents neurodegeneration in culture by eliminating microglia.
abstract: BACKGROUND
  2-Deoxy-D-glucose is an inhibitor of glycolysis, which is protective in animal models of brain pathology, but the mechanisms of this protection are unclear. We examined whether, when and how deoxyglucose protects neurons in co-culture with astrocytes and microglia. Microglia are brain macrophages, which can damage neurons in inflammatory conditions.
  
  
  METHODS
  Deoxyglucose was added to primary cultures of microglia and astrocytes from rat cortex, or neurons and glia from rat cerebellum, or the BV-2 microglial cell line, and cell death and cell functions were evaluated.
  
  
  RESULTS
  Surprisingly, addition of deoxyglucose induced microglial loss and prevented spontaneous neuronal loss in long-term cultures of neurons and glia, while elimination of microglia by L-leucine-methyl ester prevented the deoxyglucose-induced neuroprotection. Deoxyglucose also prevented neuronal loss induced by addition of amyloid beta or disrupted neurons (culture models of Alzheimer's disease and brain trauma respectively). However, deoxyglucose greatly increased the neuronal death induced by hypoxia. Addition of deoxyglucose to pure microglia induced necrosis and loss, preceded by rapid ATP depletion and followed by phagocytosis of the microglia. Deoxyglucose did not kill astrocytes or neurons.
  
  
  CONCLUSIONS
  We conclude that deoxyglucose causes microglial loss by ATP depletion, and this can protect neurons from neurodegeneration, except in conditions of hypoxia. Deoxyglucose may thus be beneficial in brain pathologies mediated by microglia, including brain trauma, but not where hypoxia is involved.
authors.forename: Anna
authors.initials: A
authors.lastname: Vilalta
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. gcb3@cam.ac.uk.
authors.forename: Guy C
authors.initials: GC
authors.lastname: Brown
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003847:Deoxyglucose / Q000494:pharmacology*; D005260:Female; D000860:Hypoxia / Q000188:drug therapy; D008297:Male; D017628:Microglia / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014947:Wounds and Injuries / Q000188:drug therapy / Q000517:prevention & control*
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D003847:Deoxyglucose