Effect of age on kainate-induced seizure severity and cell death

doi:10.1016/j.neuroscience.2008.03.082

Neuroscience

Volume 154, Issue 3, 26 June 2008, Pages 1143-1153

https://doi.org/10.1016/j.neuroscience.2008.03.082 Get rights and content

Abstract

While the onset and extent of epilepsy increases in the aged population, the reasons for this increased incidence remain unexplored. The present study used two inbred strains of mice (C57BL/6J and FVB/NJ) to address the genetic control of age-dependent neurodegeneration by building upon previous experiments that have identified phenotypic differences in susceptibility to hippocampal seizure-induced cell death. We determined if seizure induction and seizure-induced cell death are affected differentially in young adult, mature, and aged male C57BL/6J and FVB/NJ mice administered the excitotoxin, kainic acid. Dose response testing was performed in three to four groups of male mice from each strain. Following kainate injections, mice were scored for seizure activity and brains from mice in each age group were processed for light microscopic histopathologic evaluation 7 days following kainate administration to evaluate the severity of seizure-induced brain damage. Irrespective of the dose of kainate administered or the age group examined, resistant strains of mice (C57BL/6J) continued to be resistant to seizure-induced cell death. In contrast, aged animals of the FVB/NJ strain were more vulnerable to the induction of behavioral seizures and associated neuropathology after systemic injection of kainic acid than young or middle-aged mice. Results from these studies suggest that the age-related increased susceptibility to the neurotoxic effects of seizure induction and seizure-induced injury is regulated in a strain-dependent manner, similar to previous observations in young adult mice.

Section snippets

Animals

Young (2-month-old), middle-aged (12 months) and old (18 months) male C57BL/6J (B6) mice, obtained from the NIA aging colony, and FVB/NJ (FVB) mice, aged in-house, were used as animal subjects. Animal experiments were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Southern California. Every effort was made to minimize the number of

Results

We have previously demonstrated that certain strains of mice are strongly resistant to seizure-induced excitotoxic cell death in spite of similar seizure severity (Schauwecker and Steward 1997, Schauwecker et al 2000, Schauwecker 2000, Schauwecker 2002a, Schauwecker 2002b). Here we asked whether: 1) age can act as a risk factor to increase the susceptibility of mice to kainate-induced behavioral seizures and seizure-induced hippocampal cell loss; and 2) genetic susceptibility to seizure-induced

Discussion

This study used the kainate chemoconvulsant model to determine whether age is a risk factor for kainate-induced seizures and seizure-induced cell death in middle-aged and aged mice in comparison with established outcomes in young adult mice that are differentially susceptible to kainate-induced cell death. As a first step toward addressing the mechanism regulating susceptibility differences, we wanted to determine whether the variable response to kainate seizure induction and excitotoxic injury

Conclusions

In summary, our findings demonstrate that seizure susceptibility in both strains increases with advancing age. Among FVB mice, seizure-induced cell death becomes more pronounced with advancing age, while C57BL/6 mice continue to be resistant to KA-induced cell death. Future studies will need to reveal the risk factors and mechanisms responsible for differential vulnerability to glutamate excitotoxicity between these two mouse strains and the interaction with age.

Besides differences in glutamate

Acknowledgments

This work was supported by NIH grant AG025508 to P.E.S. and by the Rose Hills Foundation Research Fellowship to C.S.B. The authors wish to thank Dr. Thomas H. McNeill for thoughtful comments on the manuscript.

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¹: These authors contributed equally to this work.

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Systems neuroscienceEffect of age on kainate-induced seizure severity and cell death

Abstract

Section snippets

Animals

Results

Discussion

Conclusions

Acknowledgments

Biochem Pharmacol

Prog Brain Res

Neuroscience

Neuroscience

Exp Neurol

Mol Brain Res

Prog Brain Res

J Biol Chem

Neurobiol Aging

Brain Res Bull

Mol Brain Res

Epilepsy Res

Neurobiol Aging

Neuroscience

Epilepsy Res

Neuropharmacology

Neuroscience Lett

Epilepsy Res

Prog Neurobiol

Exp Neurol

Brain Res

Prog Neurobiol

Neurobiol Aging

Prog Neurobiol

Methods Enzymol

Brain Res

Biochim Biophys Acta

Neuroscience

Neurosci Lett

Neuroscience

Neurobiol Aging

Brain Res

Eur J Pharmacol

Electroencephalogr Clin Neurophysiol

Neuroscience

Mol Brain Res

Exp Neurol

Brain Res

Exp Neurol

Brain Res

Neuroscience

Brain Res Bull

Prog Neurobiol

Neuroscience

Brain Res

Neurobiol Dis

Lancet

Brain Res

Exp Neurol

Systems neuroscience
Effect of age on kainate-induced seizure severity and cell death