Hippocampal volume and cell density changes in a mouse model of human genetic epilepsy

Richards, Kay L., Kurniawan, Nyoman D., Yang, Zhengyi, Kim, Tae Hwan, Keller, Marianne D., Low, Jun, Ullmann, Jeremy F. P., Cole, Stacey, Foong, Samuel, Galloway, Graham J., Reid, Christopher A., Paxinos, George, Reutens, David C. and Petrou, Steven (2013) Hippocampal volume and cell density changes in a mouse model of human genetic epilepsy. Neurology, 80 13: 1240-1246. doi:10.1212/WNL.0b013e31828970ec

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Author Richards, Kay L.
Kurniawan, Nyoman D.
Yang, Zhengyi
Kim, Tae Hwan
Keller, Marianne D.
Low, Jun
Ullmann, Jeremy F. P.
Cole, Stacey
Foong, Samuel
Galloway, Graham J.
Reid, Christopher A.
Paxinos, George
Reutens, David C.
Petrou, Steven
Title Hippocampal volume and cell density changes in a mouse model of human genetic epilepsy
Journal name Neurology   Check publisher's open access policy
ISSN 0028-3878
Publication date 2013-03-01
Sub-type Article (original research)
DOI 10.1212/WNL.0b013e31828970ec
Open Access Status DOI
Volume 80
Issue 13
Start page 1240
End page 1246
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Objective: The human γ-aminobutyric acid type A (GABA A)γ2R43Q (R43Q) mutation is associated with genetic epilepsy with febrile seizures. R43Qmice 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 mm3, 95% confidence interval [CI] 0.611-0.645 vs 0.595 mm3, 95% CI 0.571-0.619). The dentate granule cell density was 30% higher in R43Q compared with control mice (553 × 103 cells/mm3, 95% CI 489-616 vs 427 × 103 cells/mm3, 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.
Keyword Genetic epilepsy
Febrile seizures
Hyperthermic seizures
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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