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

doi:10.1016/j.neuroscience.2010.01.004

Neuroscience

Volume 166, Issue 3, 31 March 2010, Pages 819-831

https://doi.org/10.1016/j.neuroscience.2010.01.004 Get rights and content

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.

Section snippets

Animals

Mice deficient in the gamma subunit of the FcγRl and FcγRlll (FcRγ−/−) were generated using homogeneous recombination, as previously described (Takai et al., 1994, Nakahara and Aiso, 2006). The transgenic mice that had a C57BL/6×129SvJ genetic background were backcrossed to C57BL/6N (B6) mice for more than 12 generations, and the progeny of those mice were used for the experiments. Littermate FcRγ+/+ mice were used as wild-type controls (described as B6 in the text). Deficiency of the FcRγ gene

Pyramidal cell death

Pyramidal cell death was mild in FcRγ−/− mice compared with the B6 mice. Moderate to severe neuronal loss was observed in the CA1 and CA3 pyramidal cell layers 24 h after the KA injection in B6 mice (Fig. 1). By contrast, neuronal loss was localized to a small portion of the CA1 pyramidal cell layer in the FcRγ−/− mice, although moderate neuronal loss was observed in the CA3 pyramidal cell layer (Fig. 1). The areas of survived neurons of B6 mice were larger than those of FcRγ−/− mice in both

Discussion

Intrahippocampal KA injection caused mild to moderate pyramidal cell loss and microglial activation in the hippocampus of B6 (wild-type) mice. By contrast, pyramidal cell loss was mild in the FcRγ−/− mice. Activated microglial cells were not detected 24 h after the KA injection. The results suggested that FcRγ has a role in microglial activation and excitotoxic neuronal death. The results are consistent with a previous study that demonstrated a role for FcRγ in neuronal death, microglial

Conclusion

This study indicates that both FcγRllB and FcRγ contribute to excitotoxic pyramidal cell death via microglial activation, oxidative stress and triggering a proteolytic cascade.

Acknowledgments

We thank the Zikei Institute of Psychiatry (Okayama, Japan), the Ministry of Health, Labor, and Welfare of Japan, and the Ministry of Education, Culture, Sports, Science and Technology.

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Cellular NeuroscienceResearch PaperFcγ receptors contribute to pyramidal cell death in the mouse hippocampus following local kainic acid injection

Abstract

Section snippets

Animals

Pyramidal cell death

Discussion

Conclusion

Acknowledgments

Cell

Exp Neurol

Neuroscience

Dev Cell

J Neuroimmunol

Curr Biol

Cell

Convergence of immunoreceptor and integrin signaling

Immunol Rev

Kainic acid induction of mossy fiber sprouting: dependence on mouse strain

Hippocampus

The hippocampal laminin matrix is dynamic and critical for neuronal survival

Mol Biol Cell

IgG-assisted age-dependent clearance of Alzheimer's amyloid beta peptide by the blood–brain barrier neonatal Fc receptor

J Neurosci

Dual role of Fcgamma receptor in transient focal cerebral ischemia in mice

Stroke

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