title: IL-1β is induced in reactive astrocytes in the somatosensory cortex of rats with genetic absence epilepsy at the onset of spike-and-wave discharges, and contributes to their occurrence.
abstract: Interleukin (IL)-1β plays a crucial role in the mechanisms of limbic seizures in rodent models of temporal lobe epilepsy. We addressed whether activation of the IL-1β signaling occurs in rats with genetic absence epilepsy (GAERS) during the development of spike-and-wave discharges (SWDs). Moreover, we studied whether inhibition of IL-1β biosynthesis in GAERS could affect SWD activity. IL-1β expression and glia activation were studied by immunocytochemistry in the forebrain of GAERS at postnatal days (PN)14, PN20, and PN90 and in age-matched non-epileptic control Wistar rats. In PN14 GAERS, when no SWDs have developed yet, IL-1β immunostaining was undetectable, and astrocytes and microglia showed a resting phenotype similar to control Wistar rats. In 3 out of 9 PN20 GAERS, IL-1β was observed in activated astrocytes of the somatosensory cortex; the cytokine expression was associated with the occurrence of immature-type of SWDs. In all adult PN90 GAERS, when mature SWDs are established, IL-1β was observed in reactive astrocytes of the somatosensory cortex but not in adjacent cortical areas or in extra-cortical regions. An age-dependent c-fos activation was found in the somatosensory cortex of GAERS with maximal levels reached in PN90 rats; c-fos was also induced in some thalamic nuclei in PN20 and PN90 GAERS. Inhibition of IL-1β biosynthesis in PN90 GAERS by 4-day systemic administration of a specific ICE/Caspase-1 blocker, significantly reduced both SWD number and duration. These results show that IL-1β is induced in reactive astrocytes of the somatosensory cortex of GAERS at the onset of SWDs. IL-1β has pro-ictogenic properties in this model, and thus it may play a contributing role in the mechanisms underlying the occurrence of absence seizures.
authors.affiliation: Dept. of Pharmacology, Istanbul Bilim University School of Medicine, Buyukdere Cad, Esentepe Kampusu, Sisli, Istanbul, Turkey.
authors.forename: Demet
authors.initials: D
authors.lastname: Akin
authors.forename: Teresa
authors.initials: T
authors.lastname: Ravizza
authors.forename: Mattia
authors.initials: M
authors.lastname: Maroso
authors.forename: Nihan
authors.initials: N
authors.lastname: Carcak
authors.forename: Tugba
authors.initials: T
authors.lastname: Eryigit
authors.forename: Ilaria
authors.initials: I
authors.lastname: Vanzulli
authors.forename: Rezzan Gülhan
authors.initials: RG
authors.lastname: Aker
authors.forename: Annamaria
authors.initials: A
authors.lastname: Vezzani
authors.forename: Filiz Yılmaz
authors.initials: FY
authors.lastname: Onat
mesh_terms: D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D058256:Brain Waves / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D004151:Dipeptides / Q000494:pharmacology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004832:Epilepsy, Absence / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000378:metabolism / Q000473:pathology*; D018709:Statistics, Nonparametric; D013787:Thalamic Nuclei / Q000166:cytology / Q000378:metabolism; D062366:para-Aminobenzoates
chemical_list: D004151:Dipeptides; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D016760:Proto-Oncogene Proteins c-fos; D062366:para-Aminobenzoates; C520022:belnacasan; D010129:4-Aminobenzoic Acid