title: Kindling modulates the IL-1beta system, TNF-alpha, TGF-beta1, and neuropeptide mRNAs in specific brain regions.
abstract: Cytokines and neuropeptides may be involved in seizure-associated processes. Following amygdala kindling in rats, we determined alterations of IL-1beta, 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-beta1, neuropeptide Y (NPY), glycoprotein 130 (gp 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 from the ipsilateral kindled amygdala. The same brain region sample was used to assay for changes of all mRNA components. The results show that the 2 h-kindled group exhibited a significant up-regulation of IL-1beta, IL-1RI, TNF-alpha and TGF-beta1 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-1beta and TNF-alpha mRNAs). IL-1R AcP I and II mRNA levels were also up-regulated in the cortical regions. No changes in IL-1beta, 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.
authors.affiliation: Division Molecular Biology, School of Life and Health Sciences, University of Delaware, Newark, DE, USA. cplatasa@prius@jnj.com
authors.forename: C R
authors.initials: CR
authors.lastname: Plata-Salamán
authors.forename: S E
authors.initials: SE
authors.lastname: Ilyin
authors.forename: N P
authors.initials: NP
authors.lastname: Turrin
authors.forename: D
authors.initials: D
authors.lastname: Gayle
authors.forename: M C
authors.initials: MC
authors.lastname: Flynn
authors.forename: A E
authors.initials: AE
authors.lastname: Romanovitch
authors.forename: M E
authors.initials: ME
authors.lastname: Kelly
authors.forename: Y
authors.initials: Y
authors.lastname: Bureau
authors.forename: H
authors.initials: H
authors.lastname: Anisman
authors.forename: D C
authors.initials: DC
authors.lastname: McIntyre
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D058966:Contactins; D003345:Corticosterone / Q000097:blood; D004594:Electrophysiology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D053577:Interleukin-1 Receptor Accessory Protein; D007696:Kindling, Neurologic / Q000235:genetics / Q000502:physiology*; D008297:Male; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017472:Receptors, Interleukin-1 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D058966:Contactins; C507766:Il1rap protein, rat; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D019006:Neural Cell Adhesion Molecules; D009478:Neuropeptide Y; D009479:Neuropeptides; D011506:Proteins; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D011333:Pro-Opiomelanocortin; D019696:Peptidylprolyl Isomerase; D003345:Corticosterone