Susceptibility to seizure-induced excitotoxic cell death is regulated by an epistatic interaction between Chr 18 (Sicd1) and Chr 15 (Sicd2) loci in mice.

Seizure-induced cell death is believed to be regulated by multiple genetic components in addition to numerous external factors. We previously defined quantitative trait loci that control susceptibility to seizure-induced cell death in FVB/NJ (susceptible) and C57BL/6J (resistant) mice. Two of these quantitative trait loci assigned to chromosomes 18 (Sicd1) and 15 (Sicd2), control seizure-induced cell death resistance.

The effects of glycemic control on seizures and seizure-induced excitotoxic cell death.

Background: Epilepsy is the most common neurological disorder after stroke, affecting more than 50 million persons worldwide. Metabolic disturbances are often associated with epileptic seizures, but the pathogenesis of this relationship is poorly understood. It is known that seizures result in altered glucose metabolism, the reduction of intracellular energy metabolites such as ATP, ADP and phosphocreatine and the accumulation of metabolic intermediates, such as lactate and adenosine.

The genetics of status epilepticus.

Many common diseases and disorders, such as hypertension, diabetes, arthritis, and epilepsy, have a genetic component with a complex genetic architecture. Evidence for a genetic influence on epilepsy emerged in twin studies that reported concordance rates consistently higher in monozygotic than in dizygotic twins (Lennox, 1951; Sillanpää et al., 1991; Berkovic et al.

Genetic influence on neurogenesis in the dentate gyrus of two strains of adult mice.

Previous studies have suggested that there is a genetic influence on the regulation of cell proliferation and survival within the hippocampus. However, the links between perturbations in neurogenesis and genomic control remain unclear. Here, we examined the impact of mouse strain on four parameters of the neurogenic program, proliferation, migration, differentiation and survival in the dentate gyrus of the hippocampus as a means of determining whether allelic variation of two independently derived mouse strains, FVB/NJ and C57BL/6J, modulates basal adult murine dentate gyrus neurogenesis.

Susceptibility to excitotoxic and metabolic striatal neurodegeneration in the mouse is genotype dependent.

Previously, we had reported that hippocampal susceptibility to the neurotoxic effects of excitotoxin administration is strain dependent [Schauwecker and Steward, Proc. Natl. Acad.

Genetic control of sensitivity to hippocampal cell death induced by kainic acid: a quantitative trait loci analysis.

Host genetic factors are likely to contribute to differences in individual susceptibility to seizure-induced excitotoxic neuronal damage. Similarly, inbred strains of mice differ in their susceptibility to the kainic acid (KA) model of seizure-induced cell death, but the genes responsible for the differences are not known. Here, we define the inheritance patterns of susceptibility to KA-induced neurodegeneration in the hippocampus by assessing 331 back-cross (N2) progeny of two inbred mouse strains, C57BL/6 and FVB/N, previously shown to display resistance and sensitivity to KA-induced cell death, respectively.

Genetic basis of kainate-induced excitotoxicity in mice: phenotypic modulation of seizure-induced cell death.

Excitotoxicity, a process in which excessive excitation of glutamate receptors results in cell death, has been implicated in a number of neurological disorders. However, the genetic characteristics and molecular mechanisms that can modulate the extent of cell death are unclear. Previously, we had reported that the extent of excitotoxic cell death is conferred by differences in the genetic background of several mouse strains.

Protection provided by cyclosporin A against excitotoxic neuronal death is genotype dependent.

Purpose: Previous studies have shown that the immunosuppressant cyclosporin A (CsA), a specific blocker of the mitochondrial permeability transition (MPT) pore, can dramatically ameliorate the selective neuronal necrosis resulting from ischemia-reperfusion, traumatic brain injury, and N-methyl-d-aspartate (NMDA)-evoked neurotoxicity. The purpose of this study was to determine whether two different immunosuppressants, CsA and FK-506, could ameliorate the neuronal damage observed after kainate-induced seizures in strains that are differentially susceptible to excitotoxin-induced cell death.

Methods: Excitotoxin-resistant (C57BL/6) or -susceptible (FVB/N) mice were administered kainate alone (30 mg/kg), CsA alone (5, 10, or 20 mg/kg), or one of the immunosuppressants (CsA, 5 mg/kg or 10 mg/kg; FK-506, 0.

Differences in ionotropic glutamate receptor subunit expression are not responsible for strain-dependent susceptibility to excitotoxin-induced injury.

Systemic administration of kainic acid in C57BL/6 and FVB/N mice induces a comparable level of seizure induction yet results in differential susceptibility to seizure-induced cell death. While kainate administration causes severe hippocampal damage in mice of the FVB/N strain, C57BL/6 mice display no demonstrable cell loss or damage. At present, while the cellular mechanisms underlying strain-dependent differences in susceptibility remain unclear, some of this variation is assumed to have a genetic basis.