Changes in hippocampal IL-15, related cytokines, and neurogenesis in IL-2 deficient mice
Changes in hippocampal IL-15, related cytokines, and neurogenesis in IL-2 deficient mice
复制标题
DOI：
10.1016/j.brainres.2005.02.010
复制
发表时间：
2005-04-18
期刊：
影响因子：
2.9
通讯作者：
Petitto, JM
中科院分区：
文献类型：
--
作者：
Beck, RD;Wasserfall, C;Petitto, JM
先前的研究表明，白细胞介素-2基因敲除（KO）小鼠表现出海马细胞结构的改变。一些证据表明，这些变化可能是由于免疫失调和/或自身免疫。因此，本研究试图比较成年IL-2 KO小鼠和野生型同窝小鼠（8-12周龄）（先前观察到海马细胞结构差异的年龄）在海马神经免疫状态测量中的差异。此外，由于IL-15与IL-2（IL-2/15 R β和γ（c））共享相同的信号转导受体亚单位，其在海马中富集并可在IL-2 KO小鼠中诱导炎症过程，因此我们试图检验IL-15在IL-2 KO小鼠海马中升高的假设。与野生型小鼠相比，IL-2 KO小鼠表现出IL-15以及IL-12、IP-10和MCP-1的海马蛋白浓度增加。然而，这些细胞因子的变化与外周循环中的水平无关，并且在IL-2 KO小鼠的海马中没有T细胞或MHCII阳性小胶质细胞增加。由于某些炎性细胞因子水平升高可能会损害海马神经发生，我们还测试了神经免疫状态的变化与IL-2 KO小鼠齿状回神经元发生减少相关的假设。与此假设相反，与野生型小鼠相比，雄性IL-2 KO小鼠在齿状回颗粒细胞层的下锥体和上锥体肢中表现出增加的神经发生，在雌性之间未观察到差异。这些研究结果表明，IL-2基因缺失改变神经免疫状态的小鼠海马通过中枢神经系统细胞产生的细胞因子的失调，在男性，这些变化与海马神经发生增加。(c)2005 Elsevier B. V.保留所有权利。
Previous studies have demonstrated that interleukin-2 knockout (KO) mice exhibit alterations in hippocampal cytoarchitecture. Several lines of evidence suggest that these variations may result from immune dysregulation and/or autoimmunity. Thus, this study sought to compare adult IL-2 KO mice and wild-type littermates (8-12 weeks of age), the age where differences in hippocampal cytoarchitecture have previously been observed, for differences in measures of neuro immunological status in the hippocampus. Furthermore, because IL-15 shares the same receptor subunits for signal transduction as IL-2 (IL-2/15R beta and gamma(c)) that are enriched in the hippocampus and may induce inflammatory processes in IL-2 KO mice, we sought to test the hypothesis that IL-15 is elevated in the hippocampus of IL-2 KO mice. Compared to wild-type mice, IL-2 KO mice exhibited increased hippocampal protein concentrations of IL-15 as well as IL-12, IP-10, and MCP-1. These cytokine changes, however, did not correlate with levels in the peripheral circulation, and there were no T cells or an increase in MHCII-positive microglia in the hippocampus of IL-2 KO mice. Since elevated levels of certain inflammatory cytokines may impair hippocampal neurogenesis, we also tested the hypothesis that changes in neuroimmunological status would be associated with reductions in neurogenesis of neurons in the dentate gyrus of IL-2 KO mice. Contrary to this hypothesis, compared to wild-type mice, male IL-2 KO mice exhibited increased neurogenesis in both the infirapyramidal and suprapyramidal limbs of the granule cell layer of the dentate gyrus, differences that were not observed between females. These findings indicate that IL-2 gene deletion alters the neuro immunological status of the mouse hippocampus through a dysregulation of cytokines produced by CNS cells, and in males, these changes are associated with increased hippocampal neurogenesis. (c) 2005 Elsevier B.V. All rights reserved.