Journal article

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

Kay L Richards, Nyoman D Kurniawan, Zhengyi Yang, Tae Hwan Kim, Marianne D Keller, Jun Low, Jeremy FP Ullmann, Stacey Cole, Samuel Foong, Graham J Galloway, Christopher A Reid, George Paxinos, David C Reutens, Steven Petrou



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 stereolog..

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Awarded by National Health and Medical Research Council of Australia

Awarded by ARC

Awarded by NHMRC

Funding Acknowledgements

The authors gratefully acknowledge Prof. Samuel Berkovic for critically reviewing the manuscript. This work was supported by the Victorian Government through the Operational Infrastructure Scheme. The authors thank the Queensland NMR Network and the National Imaging Facility for instrument access and technical support.This study was funded by the National Health and Medical Research Council of Australia enabling grant (436673) and ARC discovery project grant (DP120104112). Associate Professor Steve Petrou was a paid consultant for Bionomics P/L for several years and Bionomics owns the intellectual property related to the R43Q mouse model used in the study. S.P. acknowledges support from an NHMRC fellowship (1005050). C.A.R. acknowledges the support of an ARC Future Fellowship (FT0990628).