title: Low blood glucose precipitates spike-and-wave activity in genetically predisposed animals.
abstract: OBJECTIVE
  Absence epilepsies are common, with a major genetic contribution to etiology. Certain environmental factors can influence absence occurrence but a complete understanding of absence precipitation is lacking. Herein we investigate if lowering blood glucose increases spike-wave activity in mouse models with varying seizure susceptibility.
  
  
  METHODS
  Three mouse models were used: an absence seizure model based on the knockin of a human GABA(A) γ2(R43Q) mutation (DBA(R43Q)), the spike-wave discharge (SWD)-prone DBA/2J strain, and the seizure resistant C57Bl/6 strain. Electrocorticography (ECoG) studies were recorded to determine SWDs during hypoglycemia induced by insulin or overnight fasting.
  
  
  RESULTS
  An insulin-mediated reduction in blood glucose levels to 4 mm (c.a. 40% reduction) was sufficient to double SWD occurrence in the DBA(R43Q) model and in the SWD-prone DBA/2J mouse strain. Larger reductions in blood glucose further increased SWDs in both these models. However, even with large reductions in blood glucose, no discharges were observed in the seizure-resistant C57Bl/6 mouse strain. Injection of glucose reversed the impact of insulin on SWDs in the DBA(R43Q) model, supporting a reduction in blood glucose as the modulating influence. Overnight fasting reduced blood glucose levels to 4.5 mm (c.a. 35% reduction) and, like insulin, caused a doubling in occurrence of SWDs.
  
  
  CONCLUSIONS
  Low blood glucose can precipitate SWDs in genetically predisposed animal models and should be considered as a potential environmental risk factor in patients with absence epilepsy.
authors.affiliation: Florey Neuroscience Institute, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Reid
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004832:Epilepsy, Absence / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
chemical_list: D001786:Blood Glucose