Trinity College Institute for Neuroscience, Department of Physiology, Trinity College, Dublin 2, Ireland.
Brain Behav Immun. 2012 Jul;26(5):789-96. doi: 10.1016/j.bbi.2011.10.004. Epub 2011 Oct 24.
The glycoprotein, CD200, is primarily expressed on neurons and its cognate receptor CD200R is expressed principally on cells of the myeloid lineage, including microglia. The interaction of CD200 with its receptor plays a significant role in maintaining microglia in a quiescent state and therefore a decrease in CD200 expression in brain is associated with evidence of microglial activation. Conversely, activation of CD200R, for example using a CD200 fusion protein (CD200Fc), should result in a decrease in microglial activation. Here we assessed the effect of delivery of CD200Fc intrahippocampally on microglial activation and on long-term potentiation (LTP) in perforant path-granule cell synapses in young and aged rats. We hypothesized that the age-related changes in microglial activation would be attenuated by CD200Fc resulting in an improved ability of aged rats to sustain LTP. The data indicate that expression of markers of microglial activation including major histocompatibility complex Class II (MHCII) and CD40 mRNA, as well as MHCII immunoreactivity, were increased in hippocampus of aged, compared with young, rats and that these changes were associated with a deficit in LTP; these changes were attenuated in hippocampal tissue prepared from aged rats which received CD200Fc. Microglial activation and a deficit in LTP have also been reported in lipopolysaccharide (LPS)-treated rats and, here, we report that these changes were also attenuated in CD200Fc-treated animals. Thus the negative impact of microglial activation on the ability of aged and LPS-treated rats to sustain LTP is ameliorated when CD200R is activated by CD200Fc.
糖蛋白 CD200 主要表达于神经元，其同源受体 CD200R 主要表达于髓系细胞，包括小胶质细胞。CD200 与其受体的相互作用在维持小胶质细胞静止状态方面起着重要作用，因此，大脑中 CD200 表达的减少与小胶质细胞激活的证据有关。相反，CD200R 的激活，例如使用 CD200 融合蛋白（CD200Fc），应该会导致小胶质细胞激活的减少。在这里，我们评估了 CD200Fc 脑内给药对年轻和老年大鼠海马内小胶质细胞激活和穿通纤维-颗粒细胞突触长时程增强（LTP）的影响。我们假设 CD200Fc 的作用将减轻与年龄相关的小胶质细胞激活变化，从而提高老年大鼠维持 LTP 的能力。数据表明，与年轻大鼠相比，老年大鼠海马中包括主要组织相容性复合体 II（MHCII）和 CD40mRNA 在内的小胶质细胞激活标志物的表达以及 MHCII 免疫反应性增加，并且这些变化与 LTP 缺陷有关；这些变化在接受 CD200Fc 的老年大鼠海马组织中得到减轻。在脂多糖（LPS）处理的大鼠中也报道了小胶质细胞激活和 LTP 缺陷，在这里，我们报告 CD200Fc 处理的动物也减轻了这些变化。因此，当 CD200R 通过 CD200Fc 激活时，小胶质细胞激活对老年和 LPS 处理大鼠维持 LTP 的能力的负面影响得到改善。
