title: Blunted neurogenesis and gliosis due to transgenic overexpression of human soluble IL-1ra in the mouse.
abstract: Interleukin-1 (IL-1) is one of the most important cytokines in neuroinflammation, in acute conditions as well as during natural ageing and neurodegenerative disorders. Using a transgenic mouse strain with brain-directed overexpression of IL-1 receptor antagonist (Tg hsIL-1ra), we show that blocking IL-1 receptor-mediated activity resulted in abolishing the alterations in neurogenesis in response to acute and chronic neuroinflammation. In addition, using a novel approach to quantifying glial activation, we show that expression of the astrocyte cytoskeletal marker glial fibrillary acidic protein (GFAP) following kainic acid (KA)-induced seizures or during ageing did not change in Tg hsIL-1ra animals. Nevertheless, the astrocyte morphology showed major alterations, consisting of fragmentation of the processes in Tg hsIL-1ra mice. Similarly, although there was a higher degree of basal microglial activation in the transgenic mice than wild-type animals, there was no change following KA-induced seizures or with ageing. Taken together, our results indicate that IL-1 is crucial for the adaptability of the brain to acute and chronic neuroinflammation.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Novum, floor 5, Division of Neurodegeneration and Neuroinflammation, Karolinska Institutet, SE-141 86 Stockholm, Sweden. stefan.spulber@ki.se
authors.forename: Stefan
authors.initials: S
authors.lastname: Spulber
authors.forename: Mircea
authors.initials: M
authors.lastname: Oprica
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Marianne
authors.initials: M
authors.lastname: Schultzberg
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000276:immunology; D000375:Aging / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004660:Encephalitis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics / Q000276:immunology*; D009473:Neuronal Plasticity / Q000235:genetics / Q000276:immunology*; D009474:Neurons / Q000276:immunology / Q000378:metabolism; D012640:Seizures / Q000235:genetics / Q000276:immunology / Q000503:physiopathology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1