Elsevier

Neuroscience

Volume 137, Issue 1, 2006, Pages 301-308
Neuroscience

Systems neuroscience
Status epilepticus induces time-dependent neuronal and astrocytic expression of interleukin-1 receptor type I in the rat limbic system

https://doi.org/10.1016/j.neuroscience.2005.07.063Get rights and content

Abstract

Interleukin-1β is rapidly synthesized by glia after the induction of seizures. Recent evidence shows that endogenous IL-1β has proconvulsant actions mediated by interleukin-1 receptor type I. This receptor also mediates interleukin-1β effects on neuronal susceptibility to neurotoxic insults.

In this study, we investigated the basal and seizure-induced expression of interleukin-1 receptor type I in rat forebrain to identify the cells targeted by interleukin-1β during epileptic activity.

Self-sustained limbic status epilepticus was induced in rats by electrical stimulation of the ventral hippocampus. Interleukin-1 receptor type I immunoreactivity was barely detectable in neurons in control brain tissue. During status epilepticus, interleukin-1 receptor type I was induced in the hippocampal neurons firstly, and several hours later in astrocytes localized in limbic and extralimbic areas. Neuronal interleukin-1 receptor type I expression in the hippocampus outlasted the duration of spontaneous electroencephalographic seizure and was not observed in degenerating neurons. Astrocytic expression occurred transiently, between six and 18 h after the induction of status epilepticus and was invariably found in regions of neuronal damage.

These time-dependent, cell- and region-specific changes in interleukin-1 receptor type I expression during status epilepticus suggest that interleukin-1 receptor type I in neurons mediates interleukin-1β-induced fast changes in hippocampal excitability while interleukin-1 receptor type I receptors in astrocytes may mediate interleukin-1β effects on neuronal survival in hostile conditions.

Section snippets

Self-sustained limbic status epilepticus (SSLSE)

Male Sprague–Dawley rats (250–280g, Charles River, Calco, Como, Italy) were used in these experiments. Procedures involving animals and their care were conducted in conformity with institutional guidelines that are in compliance with national (D.L.n.116, G.U., supplement 40, February 18, 1992) and international laws and policies (EEC Council Directive 86/609, OJ L 358, 1, December 12, 1987; Guide for the Care and Use of Laboratory Animals, U.S. National Research Council, 1996). The experiments

Immunohistochemistry

IL-1RI immunoreactivity was present at barely detectable levels in the hippocampus of control brain; weakly-stained neurons were scattered in the CA1 and CA3 pyramidal cell layers (Fig. 1A, C). IL-1RI was rapidly up-regulated in the hippocampi of both hemispheres by seizures. Two hours and 6 h after the end of electrical stimulation, rats displayed synchronous EEG spiking in both hippocampi (upper traces in Fig. 1). In these rats, IL-1RI staining was enhanced in CA1 and CA3 pyramidal-like

Discussion

Electrically-induced SE consists of spontaneously recurrent EEG epileptic activity lasting for ∼24 h after the end of the electrical stimulation. Using this model, we have previously shown that seizures induce a rapid increase in the hippocampal levels of IL-1β mRNA accompanied by enhanced cytokine immunostaining in glial cells (De Simoni et al., 2000). The time-course of IL-1β induction in glia (De Simoni et al., 2000) closely overlaps with that of IL-1RI as described in this study suggesting

Conclusion

In conclusion, our findings show that seizures induce an early and lasting up-regulation of IL-1RI in neurons followed by a delayed and transient expression in astrocytes. Receptor modifications in neurons are localized in the hippocampus where seizures originate and they may mediate the well established IL-1β effects on neuronal excitability and seizures. IL-1RI expression in astrocytes may contribute to determine the extent to which glia affect neuron survival or degeneration in epileptic

Acknowledgments

We thank Dr. Pietro Veglianese for his help in confocal image acquisition and Ms Sabrina Di Fazio for her significant contribution to part of this study. This work was supported by Fondazione Mariani Onlus.

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