title: Fcgamma receptors contribute to pyramidal cell death in the mouse hippocampus following local kainic acid injection.
abstract: 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 FcgammaRIIB protein in parvalbumin neurons, whereas FcgammaRIII and FcgammaRI proteins were detected in microglial 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 plasminogen 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 FcgammaRlll 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 FcgammaRllB in parvalbumin neurons as well as FcRgamma in microglia in pyramidal cell death.
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 2-5-1 Shikatacho, Kitaku, 700-8558 Japan.
authors.forename: S
authors.initials: S
authors.lastname: Suemitsu
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: E
authors.initials: E
authors.lastname: Yokobayashi
authors.forename: S
authors.initials: S
authors.lastname: Usui
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: N
authors.initials: N
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: S
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D016923:Cell Death; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: D057134:Antibodies, Neutralizing; C485701:Fcgr1 protein, mouse; C499172:Fcgr2b protein, mouse; C485700:Fcgr3 protein, mouse; D017452:Receptors, IgG; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D010959:Tissue Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D007608:Kainic Acid