title: Hippocampal volume and cell density changes in a mouse model of human genetic epilepsy.
abstract: OBJECTIVE
  The human γ-aminobutyric acid type A (GABAA)γ2R43Q (R43Q) mutation is associated with genetic epilepsy with febrile seizures. R43Q mice in the C57Bl/6J background do not display spontaneous seizures, but are significantly more susceptible to hyperthermic seizures, providing a model with enhanced seizure susceptibility without the confounding influence of ongoing epileptic activity. Because of GABA's role in brain development, we sought to determine whether the R43Q mutation alters brain structure before the appearance of seizures.
  
  
  METHODS
  We used 16.4-tesla, high-field MRI to determine the volumes of hippocampal subregions. Histologic analysis of the same brains allowed stereology-based estimates of neuron counts to be obtained in CA1-3 and the dentate gyrus.
  
  
  RESULTS
  Morphologic changes were evident in seizure-naive hippocampi of susceptible mice. Dentate granule cell MRI determined that volume was 5% greater in R43Q mice compared with controls (0.628 mm(3), 95% confidence interval [CI] 0.611-0.645 vs 0.595 mm(3), 95% CI 0.571-0.619). The dentate granule cell density was 30% higher in R43Q compared with control mice (553 × 10(3) cells/mm(3), 95% CI 489-616 vs 427 × 10(3) cells/mm(3), 95% CI 362-491).
  
  
  CONCLUSIONS
  In a genetic epilepsy model that is both seizure-naive and carries an allele for febrile seizure susceptibility, we have determined hippocampal structural changes that may be applied as a biomarker for seizure susceptibility.
authors.affiliation: Australian Mouse Brain Mapping Consortium, The University of Queensland, Brisbane, Queensland.
authors.forename: Kay L
authors.initials: KL
authors.lastname: Richards
authors.forename: Nyoman D
authors.initials: ND
authors.lastname: Kurniawan
authors.forename: Zhengyi
authors.initials: Z
authors.lastname: Yang
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Marianne D
authors.initials: MD
authors.lastname: Keller
authors.forename: Jun
authors.initials: J
authors.lastname: Low
authors.forename: Jeremy F P
authors.initials: JF
authors.lastname: Ullmann
authors.forename: Stacey
authors.initials: S
authors.lastname: Cole
authors.forename: Samuel
authors.initials: S
authors.lastname: Foong
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Galloway
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Reid
authors.forename: George
authors.initials: G
authors.lastname: Paxinos
authors.forename: David C
authors.initials: DC
authors.lastname: Reutens
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
mesh_terms: D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid