Induction of immediate early genes, interleukin-1β and ornithine decarboxylase messenger RNA in spinal cord by seizures

Abstract

A number of studies have shown that seizures produced by a variety of stimuli such as metrazol, kindling or excitotoxin cause the induction of immediate early genes (IEG) and ornithine decarboxylase (ODC). The process is largely mediated through glutamate receptors since N-methyl-D-aspartate antagonists prevent this induction [ I ,2] and the response is localised to the site of stimulation. In this study we have investigated whether changes in gene expression occur during seizure activity in spinal cord through indirect activation of motor pathways. Seizures were induced by stereotaxic injection of kainate (1 l g ) into the nucleus basalis [3]. Cervical spinal cord and brain stem were removed at 1, 2, 4, 6, and 24 h after kainate injection, mRNA was prepared as previously described 141 and characterised by Northern blot analysis. Quantitation of mRNA was carried out by slot blot analysis and levels of c-fos, ODC and IL-1 0 mRNAs were related to 0-tubulin mRNA. Seizures were associated with a marked induction of c-fos mRNA from 1 h after injection, rising to a maximum at 6 h, where a 10-fold increase was detected. This increase was transient and decreased to control levels by 24 h. A parallel time course of induction of IL-10 mRNA and ODC mRNA was also seen in spinal cord reaching a maximum at 6 h. ODC mRNA increased 20fold at 6 h whereas IL-10 increased 10-fold. Levels of ODC mRNA in brain stem were increased 2-3-fold by kainate injection whilst levels of c-fos and IL-10 mRNA were largely unaffected. These results indicate that seizure produces an extensive induction of an IEG (c-fos), ODC and a cytokine (IL-1 0) affecting not only cortical areas responsible for initiating the seizure but also the spinal cord and brain stem through secondary activation.