Seizure expression, behavior, and brain morphology differences in colonies of Genetic Absence Epilepsy Rats from Strasbourg.
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 CaV 3.2 T-type calcium channel (R1584P) was present in all four GAERS colonies, but absent in all NEC rats.


CONCLUSIONS
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.
Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Kim L
KL
Powell
Howard
H
Tang
Caroline
C
Ng
Isabelle
I
Guillemain
Gabriel
G
Dieuset
Gabi
G
Dezsi
Nihan
N
Çarçak
Filiz
F
Onat
Benoît
B
Martin
Terence J
TJ
O'Brien
Antoine
A
Depaulis
Nigel C
NC
Jones
D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000235:genetics; D001921:Brain / Q000473:pathology*; D058256:Brain Waves / Q000235:genetics; D020747:Calcium Channels, T-Type / Q000235:genetics*; D003863:Depression / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000150:complications / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar
C509958:Cacna1h protein, rat; D020747:Calcium Channels, T-Type
Absence seizures; Behavioral comorbidities; Brain morphology; CaV3.2 R1584P mutation; Cacna1h; Genetic absence epilepsy rat from Strasbourg