title: Enhanced susceptibility to seizures modulated by high interleukin-1β levels during early life malnutrition.
abstract: Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin-1β (IL-1β) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL-1β, IL-1R1, PSD-95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL-1β and IL-1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL-1β in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL-1β and IL-1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD-95 and synapsin expression in the hippocampus. We suggest that malnutrition-induced inflammation might contribute to seizure susceptibility in the postnatal period. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150-1159, 2016.
authors.affiliation: Neuroscience Laboratory, Biomedical Research Institute, Pontifical Catholic University of Rio Grande Do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Fabrício
authors.initials: F
authors.lastname: Simão
authors.affiliation: Neuroscience Laboratory, Biomedical Research Institute, Pontifical Catholic University of Rio Grande Do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Victória
authors.initials: V
authors.lastname: Habekost Oliveira
authors.affiliation: Neuroscience Laboratory, Biomedical Research Institute, Pontifical Catholic University of Rio Grande Do Sul (PUCRS), Porto Alegre, RS, Brazil.|School of Medicine and Brain Institute (InsCer), Pontifical Catholic University of Rio Grande Do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Magda
authors.initials: M
authors.lastname: Lahorgue Nunes
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004797:Enzyme-Linked Immunosorbent Assay; D005481:Flurothyl; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology*; D007155:Immunologic Factors / Q000494:pharmacology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D044342:Malnutrition / Q000276:immunology*; D008426:Maternal Deprivation; D008565:Membrane Proteins / Q000378:metabolism; D023421:Models, Animal; D053573:Receptors, Interleukin-1 Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D012640:Seizures / Q000276:immunology* / Q000517:prevention & control; D016704:Synapsins / Q000378:metabolism
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; C000594089:IL1B protein, rat; C580803:IL1R1 protein, rat; D007155:Immunologic Factors; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D053573:Receptors, Interleukin-1 Type I; D016704:Synapsins; D005481:Flurothyl; D003345:Corticosterone
keywords: hippocampus; inflammation; interlekin-1β; malnutrition; seizures