Volume 55, Issue 12 pp. 1959-1968

Full-Length Original Research

Seizure expression, behavior, and brain morphology differences in colonies of Genetic Absence Epilepsy Rats from Strasbourg

Kim L. Powell,

Kim L. Powell

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Howard Tang,

Howard Tang

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Caroline Ng,

Caroline Ng

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Isabelle Guillemain,

Isabelle Guillemain

Grenoble Institute of Neurosciences, Inserm U836 – University Joseph Fourier, Grenoble, France

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Gabriel Dieuset,

Gabriel Dieuset

Inserm, U1099, Rennes, France

University of Rennes 1, LTSI, Rennes, France

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Gabi Dezsi,

Gabi Dezsi

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Nihan Çarçak,

Nihan Çarçak

Department of Pharmacology, Istanbul University Faculty of Pharmacy, Istanbul, Turkey

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Filiz Onat,

Filiz Onat

Department of Pharmacology, School of Medicine, Marmara University, Istanbul, Turkey

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Benoît Martin,

Benoît Martin

Inserm, U1099, Rennes, France

University of Rennes 1, LTSI, Rennes, France

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Terence J. O'Brien,

Terence J. O'Brien

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Antoine Depaulis,

Corresponding Author

Antoine Depaulis

Grenoble Institute of Neurosciences, Inserm U836 – University Joseph Fourier, Grenoble, France

Address correspondence to Nigel C. Jones, Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia. E-mail: [email protected] and Antoine Depaulis, Université Joseph Fourier, Grenoble Institut des Neurosciences, Inserm U836, Grenoble, France. E-mail: [email protected]Search for more papers by this author

Nigel C. Jones,

Corresponding Author

Nigel C. Jones

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

Kim L. Powell,

Kim L. Powell

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Howard Tang,

Howard Tang

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Caroline Ng,

Caroline Ng

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Isabelle Guillemain,

Isabelle Guillemain

Grenoble Institute of Neurosciences, Inserm U836 – University Joseph Fourier, Grenoble, France

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Gabriel Dieuset,

Gabriel Dieuset

Inserm, U1099, Rennes, France

University of Rennes 1, LTSI, Rennes, France

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Gabi Dezsi,

Gabi Dezsi

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Nihan Çarçak,

Nihan Çarçak

Department of Pharmacology, Istanbul University Faculty of Pharmacy, Istanbul, Turkey

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Filiz Onat,

Filiz Onat

Department of Pharmacology, School of Medicine, Marmara University, Istanbul, Turkey

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Benoît Martin,

Benoît Martin

Inserm, U1099, Rennes, France

University of Rennes 1, LTSI, Rennes, France

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Terence J. O'Brien,

Terence J. O'Brien

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Antoine Depaulis,

Corresponding Author

Antoine Depaulis

Grenoble Institute of Neurosciences, Inserm U836 – University Joseph Fourier, Grenoble, France

Nigel C. Jones,

Corresponding Author

Nigel C. Jones

Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia

First published: 06 November 2014

https://doi.org/10.1111/epi.12840

Citations: 59

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Summary

Objective

Originally derived from a Wistar rat strain, a proportion of which displayed spontaneous absence-type seizures, Genetic Absence Epilepsy Rats from Strasbourg (GAERS) represent the most widely utilized animal model of genetic generalized epilepsy. Here we compare the seizure, behavioral, and brain morphometric characteristics of four main GAERS colonies that are being actively studied internationally: two from Melbourne (MELB and STRAS-MELB), one from Grenoble (GREN), and one from Istanbul (ISTAN).

Methods

Electroencephalography (EEG) recordings, behavioral examinations, and structural magnetic resonance imaging (MRI) studies were conducted on GAERS and Non-Epileptic Control (NEC) rats to assess and compare the following: (1) characteristics of spike-and-wave discharges, (2) anxiety-like and depressive-like behaviors, and (3) MRI brain morphology of regions of interest.

Results

Seizure characteristics varied between the colonies, with MELB GAERS exhibiting the least severe epilepsy phenotype with respect to seizure frequency, and GREN GAERS exhibiting four times more seizures than MELB. MELB and STRAS-MELB colonies both displayed consistent anxiety and depressive-like behaviors relative to NEC. MELB and GREN GAERS showed similar changes in brain morphology, including increased whole brain volume and increased somatosensory cortical width. A previously identified mutation in the Cacna1h gene controlling the Ca_V3.2 T-type calcium channel (R1584P) was present in all four GAERS colonies, but absent in all NEC rats.

Significance

This study demonstrates differences in epilepsy severity between GAERS colonies that were derived from the same original colony in Strasbourg. This multi-institute study highlights the potential impact of environmental conditions and/or genetic drift on the severity of epileptic and behavioral phenotypes in rodent models of epilepsy.

Supporting Information

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Volume55, Issue12

December 2014

Pages 1959-1968

Seizure expression, behavior, and brain morphology differences in colonies of Genetic Absence Epilepsy Rats from Strasbourg

Summary

Objective

Methods

Results

Significance

Supporting Information

References

Citing Literature

References

Information

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Seizure expression, behavior, and brain morphology differences in colonies of Genetic Absence Epilepsy Rats from Strasbourg

Summary

Objective

Methods

Results

Significance

Supporting Information

References

Citing Literature

References

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