Fcγ receptors contribute to pyramidal cell death in the mouse hippocampus following local kainic acid injection

S. Suemitsu, M. Watanabe, E. Yokobayashi, Shinichi Usui, T. Ishikawa, Yousuke Matsumoto, Norihito Yamada, M. Okamoto, S. Kuroda

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Abstract

Recent studies have demonstrated the contribution of the gamma subunit of the Fc receptor of IgG (FcRγ) to neuronal death following ischemic injury and Parkinson's disease. We examined the role of FcRγ in hippocampal pyramidal cell death induced by kainic acid (KA). FcRγ-deficient mice (FcRγ-/-) and their FcRγ+/+ 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 FcRγ-/- mice than in B6 mice in both the CA1 and CA3. Immunohistochemical and immunofluorescent studies detected FcγRIIB protein in parvalbumin neurons, whereas FcγRIII and FcγRI proteins were detected in microglial cells. No activated microglial cells were detected 24 h after the KA injection in FcRγ-/- 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 FcRγ-/- mice. Co-injection of a neutralizing antibody against FcγRll and FcγRlll 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 FcγRllB in parvalbumin neurons as well as FcRγ in microglia in pyramidal cell death.

Original languageEnglish
Pages (from-to)819-831
Number of pages13
JournalNeuroscience
Volume166
Issue number3
DOIs
Publication statusPublished - Mar 31 2010

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Keywords

  • FcγRllB
  • FcγRlll
  • gamma subunit of FcRs
  • parvalbumin neuron

ASJC Scopus subject areas

  • Neuroscience(all)

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