Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 2-5-1 Shikatacho, Kitaku, 700-8558 Japan.
Neuroscience. 2010 Mar 31;166(3):819-31. doi: 10.1016/j.neuroscience.2010.01.004. Epub 2010 Jan 13.
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.
最近的研究表明，免疫球蛋白 G 的 Fc 受体的γ亚基（FcRγ）在缺血性损伤和帕金森病后的神经元死亡中起作用。我们研究了 FcRγ在红藻氨酸（KA）诱导的海马锥体细胞死亡中的作用。FcRγ缺陷型小鼠（FcRγ-/-）及其 FcRγ+/+同窝仔鼠（野生型，B6）接受 KA 海马背侧注射。注射后 24 和 72 小时定量分析锥体细胞死亡。与 B6 小鼠相比，FcRγ-/-小鼠 CA1 和 CA3 中的存活锥体细胞数量明显更多。免疫组化和免疫荧光研究检测到 FcγRIIB 蛋白在副甲状腺蛋白神经元中，而 FcγRIII 和 FcγRI 蛋白在小胶质细胞中检测到。在 FcRγ-/-小鼠中，KA 注射后 24 小时未检测到活化的小胶质细胞，而在 B6 小鼠中存在许多活化的小胶质细胞。KA 注射后 16 小时，B6 小鼠中硝基酪氨酸以及诱导型一氧化氮合酶和环氧化酶-2 蛋白的产生增加。此外，组织型纤溶酶原激活物和金属蛋白酶-2 蛋白增加。相比之下，FcRγ-/-小鼠的氧化应激程度和蛋白酶表达增加程度较轻。KA 与针对 FcγRll 和 FcγRlll 的中和抗体共注射可消除锥体细胞死亡和小胶质细胞活化。此外，中和抗体减少了氧化应激和蛋白酶的表达。这些观察结果表明，FcγRIIB 在副甲状腺蛋白神经元以及 FcRγ在小胶质细胞中在锥体细胞死亡中起作用。
