The type 1 interleukin 1 receptor is not required for the death of murine hippocampal dentate granule cells and microglia activation - Université de La Réunion Access content directly
Journal Articles Brain Research Year : 2008

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.

Dates and versions

hal-01198354 , version 1 (11-09-2015)

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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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