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The type 1 interleukin 1 receptor is not required for the death of murine hippocampal dentate granule cells and microglia activation

Abstract : Alterations in inflammatory process, neuronal death, and glia response have been observed under manipulation of interleukin-1 (IL-1) and subsequent signaling through the type 1 IL-1 receptor (IL-1R1). To investigate the influence of IL-1R1 activation in the pathophysiology of a chemical-induced injury to the murine hippocampus, we examined the level and pattern of neuronal death and neuroinflammation in male weanling mice exposed to trimethyltin hydroxide (2.0 mg TMT/kg, i.p.). Dentate granule cell death occurred at 6 h post-TMT as detected by active caspase 3 immunostaining and presence of lectin positive microglia. The severity of neuronal death and microglia response increased by 12–24 h with elevations in mRNA levels for TNFα and IL-1α. In IL-1R1 null (IL-1R1−/−) mice, the pattern and severity of neuronal death at 24 or 72 h post-TMT was similar as compared to wildtype (WT) mice. In both groups, mRNA levels for TNFα and MIP-1α were elevated, no significant change was seen in either IL-1α or IL-1β, and the early activation of microglia, including their ability to progress to a phagocytic phenotype, was maintained. Compared to WT mice, IL-1R1−/− mice displayed a limited glial fibrillary acidic protein (GFAP) astrocytic response, as well as a preferential induction in mRNA levels of Fas signaling components. Cumulatively, these results indicate that IL-1R1 activation is not necessary for TMT-induced death of dentate granule neurons or local activation of microglia; however, IL-1R1 signaling is involved in mediating the structural response of astrocytes to injury and may regulate apoptotic mechanisms via Fas signaling components.
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Contributor : Nicolas Alarcon Connect in order to contact the contributor
Submitted on : Friday, September 11, 2015 - 9:06:48 PM
Last modification on : Friday, January 21, 2022 - 3:27:01 AM

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G. Jean Harry, Jason A. Funk, Christian Lefebvre d'Hellencourt, Christopher A. Mcpherson, Mineyoshi Aoyama. The type 1 interleukin 1 receptor is not required for the death of murine hippocampal dentate granule cells and microglia activation. Brain Research, 2008, 1194, pp.8--20. ⟨10.1016/j.brainres.2007.11.076⟩. ⟨hal-01198354⟩



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