Kindling modulates the IL-1β system, TNF-α, TGF-β1, and neuropeptide mRNAs in specific brain regions

Cytokines and neuropeptides may be involved in seizure-associated processes. Following amygdala kindling in rats, we determined alterations of IL-1 beta, IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type I (IL-1RI), IL-1 receptor accessory proteins (IL-1R AcPs) I and II, TNF-alpha, TGF-beta 1, neuropeptide Y (NPY), glycoprotein 130 (ep 130) and pro-opiomelanocortin (POMC) mRNA levels in the parietal, prefrontal and piriform cortices, amygdala, hippocampus and hypothalamus. Messenger RNAs expression in all brain regions was determined 2 h or 3 weeks following the last generalized convulsive seizure triggered fi om the ipsilateral kindled amygdala. The same brain region sample was used to assay for changes of all mRNA component. The results show that the h-kindled group exhibited a significant up-regulation of IL-1 beta, IL-1RI, TNF-alpha and TGF-beta 1 mRNAs in all three cortical brain regions, amygdala and hippocampus. The largest up-regulation occurred in the prefrontal cortex (about 30-fold induction for IL-1 beta and TNF-alpha mRNAs). IL-1R AcP I and II mRNA levels were also up-regulated in the cortical regions. No changes in IL-1 beta, IL-1RI or TNF-alpha mRNA levels occurred in the 3 week-kindled group. NPY mRNA levels increased in the hippocampus, prefrontal and piriform cortices in the 2 h-kindled group, while IL-1Ra, gp 130, or POMC mRNA levels did not change in any group. The overall profile of mRNA changes shows specificity of transcriptional modulation induced by amygdala kindling. The data support a role of cytokines and NPY in the adaptive mechanisms associated with generalized seizure activity, with implications for neuroprotection, neuronal dysfunction and vulnerability associated with epileptic activity. (C) 2000 Elsevier Science B.V. All rights reserved.