Fcgamma RECEPTORS CONTRIBUTE TO PYRAMIDAL CELL DEATH IN THE MOUSE HIPPOCAMPUS FOLLOWING LOCAL KAINIC ACID INJECTION

摘要

Recent studies have demonstrated the contribution of the gamma subunit of the Fc receptor of IgG (FcRgamma) to neuronal death following ischemic injury and Parkinson's disease. We examined the role of FcRgamma in hippocampal pyramidal cell death induced by kainic acid (KA). FcRgamma-deficient mice (FcRgamma-/-) and their FcRgamma+/+ littermates (wild type, B6) received an injection of KA into the dorsal hippocampus. Pyramidal cell death was quantified 24 and 72 h after the injection. The number of survived pyramidal cells was significantly larger in FcRgamma-/- mice than in B6 mice in both the CA1 and CA3. Immunohistochemical and immunofluorescent studies'detected FcyRIIB protein in parvalbumin neurons, whereas FcyRIII and FcgammaRI proteins were detected in micro-glial cells. No activated microglial cells were detected 24 h after the KA injection in FcRgamma-/- mice, whereas many activated microglial cells were present in B6 mice. The production of nitrotyrosine as well as of the inducible nitric oxide synthase and cyclooxygenase-2 proteins, increased by 16 h after the KA injection in B6 mice. In addition, tissue plasmin-ogen activator and metalloproteinase-2 proteins increased. By contrast, the magnitude of oxidative stress and the increase in protease expression were mild in FcRgamma-/- mice. Co-injection of a neutralizing antibody against FcgammaRll and FcgammaRIII with KA abolished pyramidal cell death and microglial activation. In addition, the neutralizing antibody reduced oxidative stress and expression of proteases. These observations suggested a role for FcyRIIB in parvalbumin neurons as well as FcRgamma in microglia in pyramidal cell death.