Susceptibility to hippocampal kindling seizures is increased in aging C57 black mice

Kurt R Stover,Stellar Lim,Terri-Lin Zhou,Paul M Stafford,Jonathan Chow,Haoyuan Li,Nila Sivanenthiran,Sivakami Mylvaganam,Chiping Wu,Donald F Weaver,James Eubanks,Liang Zhang

doi:10.1016/j.ibror.2017.08.001

Kurt R Stover, Stellar Lim + Show 10 more

Open Access

https://doi.org/10.1016/j.ibror.2017.08.001

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Abstract

The incidence of seizures increases with old age. Stroke, dementia and brain tumors are recognized risk factors for new-onset seizures in the aging populations and the incidence of these conditions also increased with age. Whether aging is associated with higher seizure susceptibility in the absence of the above pathologies remains unclear. We used classic kindling to explore this issue as the kindling model is highly reproducible and allows close monitoring of electrographic and motor seizure activities in individual animals. We kindled male young and aging mice (C57BL/6 strain, 2–3 and 18–22 months of age) via daily hippocampal CA3 stimulation and monitored seizure activity via video and electroencephalographic recordings. The aging mice needed fewer stimuli to evoke stage-5 motor seizures and exhibited longer hippocampal afterdischarges and more frequent hippocampal spikes relative to the young mice, but afterdischarge thresholds and cumulative afterdischarge durations to stage 5 motor seizures were not different between the two age groups. While hippocampal injury and structural alterations at cellular and micro-circuitry levels remain to be examined in the kindled mice, our present observations suggest that susceptibility to hippocampal CA3 kindling seizures is increased with aging in male C57 black mice.

Highlights

Old age is associated with high incidence of seizures and epilepsy, and temporal lobe epilepsy is the most common type of seizure disorder in aging/aged populations
Examples of stage 5 motor seizures evoked from a young mouse and an aging mouse are shown in Supplementary Video 1 and 2
We plotted the mean seizure scores vs. the number of hippocampal stimulation to reveal a general trend of motor seizure progression in the young and aging mice

Summary

Introduction

Old age is associated with high incidence of seizures and epilepsy, and temporal lobe epilepsy is the most common type of seizure disorder in aging/aged populations. The hippocampus is known to undergo structural and functional alterations during aging (Burke and Barnes, 2010; Bartsch and Wulff, 2015) These include a loss of subgroups of hippocampal GABAergic interneurons (Shetty and Turner, 1998; Cadacio et al, 2003; Vela et al, 2003; Shi et al, 2004; Stanley and Shetty, 2004; Potier et al, 2006; Kuruba et al, 2011; Smith et al, 2000; Stanley et al, 2012; Spiegel et al, 2013) and an increase in hyperactive or hyperexcitable responses of hippocampal CA3 neurons in aging/aged animals (Vreugdenhil and Toescu, 2005; Wilson et al, 2005; Patrylo et al, 2007; Kanak et al, 2011; Lu et al, 2011; ElHayek et al, 2013; Spiegel et al, 2013; Moradi-Chameh et al, 2014; Simkin et al, 2015; Villanueva-Castillo et al, 2017). In light of these findings and classic kindling as a widely used model of temporal lobe epilepsy

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Conclusion