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Kindling susceptibility and genetic seizure predisposition in inbred mice
1Department of Neurology, Emory University School of Medicine, Atlanta, Georgia.
Abstract:
Olfactory bulb kindling rates were studied in two inbred strains of genetically seizure-prone mice (DBA/2 and El) and in three non-epileptic inbred strains [C57BL/6 (B6), ddY, and C3H/He (C3H)]. None of the DBA/2 mice had been stimulated to seizure before or during the kindling and all mice were studied at 4-6 weeks of age, before development of spontaneous or movement-induced seizure activity in the El strain. The audiogenically seizure-susceptible DBA/2 mice required the fewest number of stimulations to reach stage 5 seizure (mean +/- SE = 4.0 +/- 0.6). The nonepileptic C3H mice required the most stimulations to reach stage 5 seizures (22.6 +/- 1.4). Kindling rates for B6 (9.6 +/- 0.6), El (14.8 +/- 1.1), and ddY (18.5 +/- 1.0) strains were intermediate, and the kindling rate for each strain was significantly different from that of the other strains. These findings show that the seizure-susceptible El mouse kindles more rapidly than the genetically similar but nonepileptic ddY control and suggest that an inherited seizure susceptibility accelerates the kindling rate. Nonepileptic B6 mice kindled more rapidly than El mice, however, suggesting that genetic factors other than those that influence seizure susceptibility are of primary importance in the determination of the kindling rate.
Insights
Seizure susceptibility in mice influences olfactory bulb kindling rates. Genetically seizure-prone El mice kindled faster than non-epileptic controls, but other genetic factors also impact kindling speed.
Area of Science:
- Neuroscience
- Genetics
- Epilepsy Research
Background:
- Olfactory bulb kindling is a model for studying epilepsy development.
- Genetic factors play a role in seizure susceptibility and progression.
Purpose of the Study:
- To investigate olfactory bulb kindling rates in different inbred mouse strains.
- To determine the influence of inherited seizure susceptibility on kindling rates.
Main Methods:
- Electrical stimulation of the olfactory bulb was used to induce seizures in mice.
- Kindling rates were measured by the number of stimulations required to reach stage 5 seizures.
- Five inbred mouse strains were studied: DBA/2, El, C57BL/6 (B6), ddY, and C3H/He (C3H).
Main Results:
- Audiogenically seizure-susceptible DBA/2 mice showed the fastest kindling (4.0 stimulations).
- Non-epileptic C3H mice exhibited the slowest kindling (22.6 stimulations).
- El mice (seizure-prone) kindled faster than their non-epileptic ddY counterparts, suggesting inherited seizure susceptibility accelerates kindling.
Conclusions:
- Inherited seizure susceptibility appears to accelerate olfactory bulb kindling rates.
- Genetic factors beyond seizure susceptibility significantly influence the determination of kindling rates.
- Further research is needed to elucidate the specific genetic mechanisms underlying differential kindling rates.